Metropolis, three months later. Clark Kent (under the influence of the red kryptonite ring) has becomes a criminal, heisting banks, going to night-clubs, and living under the alias 'Kal'. But he comes into conflict with not only his Kryptonian-marked chest, but a ruthless and greedy gangster, named Morgan Edge, who wants an ever increasing percentage of the stolen loot, and also begins to suspect Clark's alien origins. Meanwhile, Lex Luthor is declared dead, but he is living with the weird Louis Leery Jr. in an isolated desert island. Back in Smallville, Dr. Helen Bryce comes to his funeral and meets Lionel Luthor in the mansion where secrets are disclosed. Lana Lang and Jonathan Kent try to bring Clark back to Smalville. Unsucessful after Lana's pleas to Clark, Jonathan makes contact in the cave with the spirit of Jor-El who imbues Jonathan with Kryptonian super-powers to combat Clark and bring him home... in exchange for a price. Also, Chloe enjoys her new job at the Daily Planet, while tailing Lana during her search for Clark.

Lex returns to Smalville and the Lex mansion, and invites Dr. Helen Bryce for a second honeymoon while trying to find out if it was her or his father who attempted to kill him. Meanwhile, Clark also returns to Smallville and the Kent farm, but Morgan Edge finds him and threatens to kill Jonathan and Martha in to get what Clark stole from Lionel Luthor's safe, which is the stolen vial of Clark Kent's blood. With the financial status of the Kent family in dire straights, the farm is sold in an auction, but there is a surprise in the end. Also, Lana tries to declare her love for Clark, but he rejects her love out of fear that she may discover his secret. Clark also returns to Smallville High and to the Torch newspaper under Chloe who continues to investigate Clark's origins.

When Lana is attacked by her obsessed school pal Jake Pollan in the deserted swimming pool of Smallville High School, he is mortally shot by an unknown shooter. Meanwhile, Lex Luthor joins Luthor Corp. and his father, Lionel, requires a $50 million life insurance from him which increases Lex's suspicions. Clark investigates the murder of Jake, and finds that the criminal is Jake's friend Van McNulty, who is killing people affected by the meteor rock radiation, and Lex is the next in his death list. When Clark saves Lex, Van sees that he is special and includes Clark in his bill, and learning of his vulnerability, the growingly paranoid and racist Van concocts and shoots Clark with a kryptonite bullet, and then decides to go after Lana for her association with Clark. Also, Chloe discovers that Lionel has taken all her research documents of Clark after discovering that she has begun investigating Lex.

Clark Kent has a strangely realistic nightmare with him being romantically involved with Lana, Lex discovering his secret, and a girl called Sara Conroy being chased by a weird, red-robed creature called The Traveller. When Clarks wakes up, he learns that was was asleep - for the last 36 consecutive hours. Clark finds that Sara has just moved with her uncle and tutor Nicholas Conroy to the house on the next door that belonged to Lana. Intrigued with the situation, he visits Sara with Lana, and Clark sees that the teenage girl has been in coma for the past six years, increasing the mystery. Clark decides the the solution is literally in his dreams. In Metropolis, Lionel demands that Lex take a psychological evaluation prior to increasing his work responsibilities, but for some unknown reason, Lex refuses.

Clark's future boss at the Daily Planet shows up; Perry White, but this time around he's a dirt bag reporter working for the tabloids.

Clark has downloaded the memories of Jor-El to solve a case that is related to Lana Lang's relative.

After being hit in the forehead by a snow globe containing flakes of meteor rocks in a struggle at a local carnival, the teenager Seth Nelson is given an M.R.I. giving him magnetic abilities. He uses his powers to date and manipulate Lana who is starting to distance herself from Clark by trying to make him jealous. Meanwhile, a snoopy investigator hired by Lex intrusively breaks in The Torch and finds that Chloe Sullivan is examining deeply the life of Lionel Luthor. Lex offers his protection to Chloe to help him investigate his father's past if he had anything to do with a apartment tenement fire that killed Lionel's parents.

While Lex continues to investigate the dark past of his father, he meets Morgan Edge with a new face after plastic surgery, and collects evidence to send Lionel Luthor to prison for the murder of his parents. However, a hit man tries to kill Lex in the mansion, but he escapes to Kent Farm. Clark goes to the mansion to retrieve the evidence against Lionel from the safe and finds that there is no hint of the claimed attempt against Lex's life. When Lionel goes to the Kent Farm and tells that Lex is paranoid and delusional over the death of Lex's infant brother years ago, Jonathan and Martha question his sanity. Clark decides to investigate deeper to see if his friend is delusional or there is an evil plot against him. As it turns out, the answer is literally... both. Although Morgan Edge is indeed alive and after both Lex and Clark, Lex's paranoia is real, which leads to him injuring Lana after he suspects her to be a part of the conspiracy against him. Clark then tries to stop Lex from killing Morgan, and in so doing is forced to reveal his secret to Lex.

Lex is committed to the Belle Reve Sanitarium for the criminally insane by Lionel who forces the shrink, Dr. Claire Foster, to submit Lex to an experimental electroshock therapy technique to erase his memory and forget his past events. Clark visits Lex and after finding out, decides to try to save his friend, despite protests from Jonathan and Martha that Clark's secret is known by Lex. But three of Clark's adversaries reside in Belle Reve. They are the arrogant, power-stealing Eric Summers (from episode "Leech"), the angry, meteor-rock mutant racist Van McNulty (from episode "Extinction") and the double-clone Ian Randall (from episode "Dichotic") who join forces to attack him so Eric can steal Clark's powers again and and escape from the asylum. Meanwhile, Lana begins to distance herself from Clark while she's attending physical therapy to recover from her broken leg with the support of a charming patient named Adam Knight (Ian Somerhalder).

While looking for a birthday gift for Martha at a local jewelry store, Clark intervenes when two thieves try to rob the place using the powerful scream of Nathan Dean (Micah Alberti), a meteor-rock mutant with the ability to project ear-splitting screams. The combination of the scream with a bijouterie of kryptonite deflecting Clark's heat vision back to his face makes Clark blind. Without this sense, his hearing uncontrollably increases. One of the criminals, Masterson (William MacDonald) is arrested. Nathan kidnaps Pete to force his mother, Judge Abigail Ross (Felecia M. Bell), to release Masterson. Meanwhile, the blind Clark listens to a phone conversation between Chloe and Lionel Luthor about Lex and himself. After Clark informs Lex about his father's intentions for them, Chloe is mistakenly taken as Lex's informer and she gets fired from her intern job at the Daily Planet by Lionel.

After leaving an article full of denunciations about the "Summerholt Neurological Institute" with her former colleague of the Daily Planet, Max Taylor, Chloe is chased by Clark Kent who tries to run her down with his truck. He claims that he had received an e-mail just before his action. Later, Lana also receives an e-mail from the same address and tries to kill Chloe on the steps of Smallville High, who is saved by Adam Knight. Clark and Chloe, with a little help from Lex, investigate the mysterious e-mail origin, and they discover that Molly Griggs, a former patient of the unethical Dr. Garner, is using her meteor-rock abilities to force people to kill through a hypnotic suggestion in her e-mails. Meanwhile, Adam moves to Smallville to be close to Lana despite that nobody knows anything about him. Also, Lex makes contact with Dr. Garner and threatens to expose his unethical practices unless he helps him regain his memory of the last seven weeks.

Jordan Cross is a new transfer student to Smallville High School who has a frightening ability: when he is touched by another person, he immediately sees how he or she will die. When Clark saves the suicidal Coach Altman from death, the future of other people changes, including Lana's. Jordan also learns Clark's secret after he physically bumps into him. Meanwhile, Chloe finds that Adam is injecting himself with some kind of experimental medication, while his increasingly erratic behavior troubles Lana. When Jordan touches Adam, he tells Lana that Adam had already died. Also, Lex continues to investigate his past to regain his memory.

While returning home after leaving Jonathan Kent in the hospital recovering from a heart attack, the truck of Martha and Clark is almost hit by two cars racing in the road. For the greatest surprise and deception of Clark, one of the drivers is Pete Ross, who has become the friend of the bad element Jason Dante whom is using meteor-rock synthetic fuel to win at drag races. Pete does not accept Clark's advice and gets into serious trouble when Dante wants $20,000 of losses after thinking Pete betrayed him to the police. Meanwhile, Lex investigates the prominent Dr. Lia Teng about her research of blood platelet with Adam Knight, and Lana feels threatened by the mysterious dark secret of Adam after finding out that he "died" of a rare liver disease and learns about the mysterious blood platelet drug he is taking to keep himself alive.

While in an elevator at Luthor Corp with another girl during a class field trip, Clark is forced to use a few of his abilities when the cable of the elevator accidentally breaks and in the process, the student, Alicia Baker, witnesses Clark's ability of heat vision and punching through steel and in return, Alicia 'teleports' herself and Clark out of the elevator. Clark confides his secret to Alicia who confides her secret of being a meteor-rock mutant with the ability of teleportation. Soon, Clark and Alicia start to get closer and he starts to really think that Alicia could be the one for him. But Alicia on the other hand, turns out to be an obsessed sociopath who wants Clark... NO MATTER WHAT! When Clark starts to realize Alicia's obsession with him, he decides to put an end to their brief relationship. But Alicia won't settle for second and sets off to kill Clark's true love Lana. Elsewhere, Lana finds a journal that Adam has and finds out that he has been spying on her and Clark... under orders from Lionel. So, Lana turns to Lex for help with this situation.

When Jonathan goes to Smallville Medical Centre for a physical examination, his doctor diagnoses arterial blockage and recommends a triple bypass heart surgery procedure. Meanwhile, Vince Davis, the older brother of Clark Kent's friend Garrett Davis, needs a liver transplant - but does not receive one and he dies. His body is sent to Metropolis to be the next test subject of Lionel's experiment by Dr. Lia Teng, who injects his dead body with experimental blood platelets and revives him. When Vince gets sick again (because he needs the life-sustaining blood injections on a daily basis), the unstable Garrett loses control and becomes a threat to the patients, employees, and visitors of the hospital by showing up at the hospital with a kryptonite-infused bomb strapped to himself, threatening to blow himself up unless his brother receives a new liver transplant. Clark must try to find a way to defuse the situation during Jonathan's heart surgery, while the overzealous Sheriff Adams wants to kill Garrett in any way possible... even at the expense of the hostages. Meanwhile, Chloe does some investigating for Lex of Dr. Teng and learns about the mysterious blood platelet serum she's manufacturing and about the first test subject: Adam.

While working as a volunteer with Pete at Smallville Youth Center, Clark receives a distress phone call from Lana, who is shot by Adam. His further investigation shows that the call was made from the future because of a time/space porthole created by a massive electrical surge from a downed power line fitted with meteor rocks, during a coming thunderstorm. Clark must try to save Lana and change the future. Meanwhile, Lionel Luthor shuts down the obscure Merton Laboratory and the research that Dr. Lia Teng is developing with blood platelet, which were finally revealed to have been developed from the vial of Clark Kent's blood. Adam becomes aware that he has less than 12 hours to be injected with the serum, otherwise he will die. He escapes, kills Dr. Teng and her whole team, and Lex is framed as responsible for the mass murder. Adam then sets out to find Lana to know if she still has an extra vial of serum for him. Lex later meets with an FBI agent, named Frank Loder, who enlists his help to bring down Lionel Luther, who also confides in an associate of his about his research and reveals the reason for it: Lionel himself is dying from a rare liver disease.

While on the roof of the barn, Jonathan is contacted though the octagonal key and Clark saves him from a fall. Clark goes to the Kawatche caves with the key trying to find an explanation for what happened, when Lionel Luthor unexpectedly appears and expresses his suspicion towards Clark. Lionel goes to New York and secretly meets with Dr. Virgil Swann and proposes an association to investigate Clark. Meanwhile, the FBI is revealed to have bugs in Lex's mansion for a surveillance to obtain evidence against Lionel, and Clark becomes a suspect due to the interest of Lionel in the apparently simple "farm boy". Later, agents, led by Frank Loder, arrive at the Kent farm to search it for the missing octagonal key, leading Clark to mistakenly believe that Dr. Swann betrayed him to Lionel. Meanwhile, Lana cannot seem to make up her mind whether she wants to stay with Clark or not.

Chloe visits a former friend of her father in Luthor Corp. to know if he is blacklisted, since all his applications are not accepted and he is not able to find a job. She steals his security card and breaks in the Luthor Corp. laboratory trying to find evidence. But she gets accidentally exposed to a meteor-rock gas which gives her the ability to makes people tell the truth whenever she gets in close contact with them, thus exposing their innermost secrets. Chloe uses her new ability to explore her curiosity of journalist, hurting people, including her history teacher, Martha, Lana, and Pete, thus showing the dangerousness of the absolute truth when she attempts to question Lionel about his criminal past, and she gets more suspicious about Clark when she learns that he is the only one immune to her 'truth' powers. But when Chloe falls ill from the side affects, Clark risks his secret becoming known by trying to save her by trying to find the scientist responsible for the kryptonite gas concoction. Meanwhile, Lex continues to uncover evidence against his father to find the grounds for the FBI to arrest him on.

Lex believes that he needs his memories back,but Clark can't take the risk of his secret being exposed.

Lionel calls Professor Joseph Willowbrook to the Kiwatche caves to show a recently found ancient object. Professor Willoebrook brings his assistant Jeremiah Holdsclaw, who takes the relic from the hands of Lionel. It transforms in a knife and makes Jeremiah as powerful as Clark. He runs away from Lionel's security men with the mythic knife. Professor Willowbrook insists that Clark is Namam, the man who fell from the stars, and in accordance with the Indian prophecy, that knife belongs to him and could be destroyed only by his greatest enemy. Jeremiah thinks that the enemy is Lionel and makes plans to kill him. Meanwhile, Lana decides to move to Paris to be away from Clark and make a fresh start. Also, a troubled Pete reveals to Chloe that his parents have decided to get a divorce.

Clark Kent decides to disclose his secret to Lana to avoid her from traveling to Paris, and he invites her for dinner at the Kent farm. But things take a turn when the dangerous teenager Emily Eve Dinsmore, the six-year-old girl (from the episode 'Accelerate') had matured into a grown-up and still obsessed with Lana, escapes from the institute where she is interned. She kills the new owner of Talon and kidnaps Lana. Meanwhile, Chloe joins forces Lex trying to find evidence to send the powerful Lionel to prison for the murder of Lex's grandparents. Elsewhere, Pete is threatened by the corrupt FBI agent, Frank Loder, who is still trying to find what he knows about Clark. Clark then decides against telling Lana his secret after Pete reveals to Clark about the pain of the ability to keep his secret and Pete decides to move away from Smallville to live with his now-divorced mother in Wichita.

At the Kent farm, Clark Kent is surprised in the middle of the night by a naked young woman claiming that she is Kara from Krypton, and asking him to go with her somewhere through the Kawatche caves to be "re-born" with the spirit of Jor-El. Kara also forces Jonathan to reveal the secret deal he made with Jor-El at the beginning of the season. Meanwhile, Clark decides to testify against Lionel to keep him in prison. Lionel sends a key of the secret chamber in the Luthor Mansion to Clark where he finally discovers the reason for the last three years of Lex's personal investigation of him, and he ends his friendship with Lex. Agent Loder continues investigating Clark's origins, until Kara finds him eavesdropping on the Kents and she eliminates Loder for good. Also, Lana leaves for Paris and Chloe and her father are included in the witness protection program. Events come full circle as Jonathan unsuccessfully tries to stop Clark from traveling through a dimensional gateway in the cave wall, Martha observes a Kryoptonia symbol that appears in a open field, Lex is alone in the mansion when he had a drink of brandy which is poisoned, Chloe and her father arrive at a FBI safe house... which explodes with them still inside, and Lionel accepts his new look in prison, but satisfied knowing that his revenge against all those involved with his incarceration has been accomplished.