Lex gets wrapped up in a sex/murder scandal. Clark gets Lionel's help to get Lex out of trouble. Lana meets Jason's mother, whom she has seen before in a dream, which was set in the 1600s.

When Lana is attacked in her apartment and Jason in his car by an invisible being, everyone believes that Alicia Baker was responsible, except Clark. However after a series of circumstances, Clark begins to doubt Alicia's innocence to the mysterious attacks. Alicia tells Clark that she'll offer to prove her innocence if Clark reveals his own superpowers, but Clark refuses. So, Alicia secretly shows Chloe the abilities of Clark, expecting people to leave them both alone. But elsewhere, Lois discovers that the real culprit of the attacks is the deranged Tim Westcott who's jealous of Alicia's abilities which leads to him murdering her, and then goes after Clark. Meanwhile, Genevieve Teague arrives back in Smallville and approaches Lex Luthor to get his help to separate her son Jason from Lana.

As if Lois Lane didn't make enough of a nuisance of herself now living at the Kent farm, she brings in Einstein, a golden retriever, who is the latest victim to be hit by her car, and she meanly calls him 'Clarky', while Clark, kind as ever, hopes to keep him as a pet if the owner isn't found, which his parents hope. Clark soon finds out it's a surviving dog of an experiment to give canines superpowers with daily injections of steroids mixed with meteorite fragments (kryptonite) produced at LuthorCorp, which Lex insists to Clark that the project was abandoned after animal activist protests, thinking they were all put down. Only later Clark finds out, the hard way, the dog and a Rothweiler are abused by evil Josh Greenfield and his kid brother Zack, who run the Smalville animal shelter and abuse dog whistles to control the super-dogs as weapons for robberies. Meanwhile, Jason and his secretive and manipulative mother, Genevieve, are revealed to know more about Lex and his apparently reformed father Lionel, while Lana and Chloe all take a keen interest in the relevance of the Teague and Lang family trees, which have common roots in countess-witch Isobel's French place of origin.

In the middle of the night on the road, a young pregnant woman is going into labor while the father of her child drives, when she suddenly glows and implodes, while the guy stops the car and runs for his life. Lana and Clark are driving a truck along the same road and find a baby in the crater created by the explosion. They take the baby to the hospital, and the Kent family temporarily guards him, who is connected to Clark. Lana and Clark give the name of Evan, and on the next day, he becomes a teenager, precociously aging. The scientists of Lex study the case and conclude that the boy needs a transfusion of the bone marrow of his unknown father, if he can be found, and even then... Clark tries to save Evan. Meanwhile, Genevieve Teague has a meeting with Lionel Luthor and threatens to hurt Lex, in case the missing stone from China is not delivered to her. But Lionel soon turns the tables on Genevieve by poisoning her (the same way he unsuccessfully tried to poison Lex in the previous season) and threatens not to give her the antidote unless she gives him the second missing stone whom she in fact stole from the murdered Bridget Crosby.

On the last day of Smallville High before graduation, the emotionally disturbed and frustrated photographer of the Torch, Brendan Nash, feels rejected by the Universities and decides to abduct some schoolmates to stay with him forever in a replica of the school. He uses his power of 'Medusa Touch' of turning people into stone by mere touch, and brings Lana, Chloe, and other successful schoolmates to the place. While Clark teams up with the nosy Lois to find the other students, he also talks with Jonathan and Martha over his college choices after graduation. Meanwhile, Genevieve and Jason Teague kidnap Lionel and Lex Luthor and hold them hostage in a remote mountain cabin and torture both of them to try to retrieve the second mystical stone that Lionel took from them.

When Lana (possessed by Isobel) kills Genevieve Teague by stabbing her with one of the Kryptonian Knowledge Crystals after she attempts to steal it, it triggers a cosmic event that not only severs Lana's link to the spirit Isobel but also sends meteorites from deep space toward Earth and Smallville. At the graduation ceremony for Smallville High, the military arrives to evacuate the town after news that another meteor shower is imminent. Fearing he has a link to the meteorites, Clark goes to talk to the spirit of Jor-El, who informs him that his only hope is to unite the knowledge crystals in the cave. With time running out, Clark sets about locating the final two crystals as meteorites reign down upon Smallville. Lana gives Clark the third stone they recovered from China, which was in her possession all this time, while the second stone is on Lionel's person, which activates. Lex offers to protect Lana and have her flown to New York City, but she gets caught in the meteor shower while riding in a helicopter. Lois manages to get out of Smallville in time, but Chloe stays behind to follow Clark who retrieves the final one from Lionel which hits them with a burst of energy driving him comatose. Chloe helps Clark retrieve the final stone from the Luthor mansion safe after he is immobilized by kryptonite, and helps him escape from Lex. Clark manages to unite all three stones, which transports him to the wild tundra of the frigid North Pole...