Martha Kent injures mind-reading Ryan in an auto accident, and he fakes amnesia to get away from his criminal step-parents. His step-parents hatch an elaborate plan to steal him back and use his abilities to rob Lex Luthor.

Clark saves Lana from the tornado, leading Lana to be suspicious of Clark. While protecting Clark's secret, Jonathan gets trapped with reporter Roger Nixon in an underground mausoleum. Lex and Clark search for Jonathan.

As Clark has finally begun dating Lana, Helen Bryce cancels her wedding to Lex after being told to by Lionel. But later, Helen realizes that she loves Lex and they finally get married. Meanwhile, Jonathan and Martha are thrilled to learn Martha is pregnant. The memory/spirit of Jor-El speaks to Clark via the spaceship, telling him he must leave Smallville, his parents and friends to fulfill his destiny. Clark decides to destroy the spacecraft, and the spirit of Jor-El with it, by using Lionel's kryptonite-made hexagon key that he made a copy of off the late Dr. Walden, in order to use it on the cave wall to learn the kryptonian markings. Clark, with Pete's help, steals the key and uses it to activate the spaceship, knowing the kryptonian radiation will destroy the ship. The ship does explode, but the shock wave injures Jonathan and Martha, causing her to miscarry. Chloe, jealous of Clark and Lana's blossoming romance, accepts Lionel's proposal to investigate Clark and gets the job at the Daily Planet. Clark, grief-stricken at the injury he caused his mother, puts on the red kryptonite ring and heads out of town on a motorcycle, planning never to return. Elsewhere, Lex, flying off on his honeymoon, wakes up alone on the airplane that is about to crash in the ocean...

Three months later. Lois Lane, the second cousin of Chloe Sullivan, arrives in Smallville trying to find the missing Clark Kent to help her to find Chloe's murderer. After being struck by a mysterious ray, she loses control of her car, and finds Clark naked with amnesia in a cornfield. She brings him to Smallville Medical Center, where Martha is with Jonathan Kent, who has been in an irreversible coma. Martha brings Clark back to the farm, expecting him to retrieve his memory. However, Clark is completely dehumanized, having been taken over by his alter-ego Kal-El, whose mission is to find three Kryptonian crystals to assemble into one. Meanwhile in Paris, Lana Lang has an American boyfriend, a young man named Jason Teague, and is having a good time with him, until things take a turn when she gets hit with a mysterious spiritual force containing the spirit of a long-dead witch. Elsewhere, Lex is struggling to recover from being poisoned as he travels to bring an ancient object retrieved from an excavation in Egypt which Clark/Kal-El is also after and uses his flying abilities to steal the crystal... in midair. Also, Lois visits the imprisoned Lionel to talk with him about Chloe, while Martha has a meeting with an associate of Virgil Swan's, named Bridget Crosby, who gives her a new type of kryptonite to combat Clark/Kal-El.

An experiment with heated (black) kryptonite at Luthorcorp causes an explosion which badly wounds Dr. Sinclair, the scientist in charge, and creates a molecular copy of Lex which has the evil side of his personality. While the real Lex shows Clark the experiment was to create far stronger crops, the evil one gives Sinclair a fatal injection in hospital after questioning him. Fearing an effect on himself, 'Evil Lex' locks the good Lex up wearing an iron mask and sets out ruining lives in Smallville, such as closing The Talon when Lana refuses to be his girlfriend, and taunting Lionel Luthor badly enough to make him turn away from charity. When Chloe shows Clark proof on hospital video recordings there must by two Lex's, Super-boy is duped into telling the fiend everything, believing him to be the real one, so the Clark family and Chloe become his prime targets, and he knows about green kryptonite and its affect on Clark.

Gabriel Duncan is a deranged teenager who breaks in the control room of a nuclear silo in Smallville, kills the two security guards, and starts the launch sequence to send one missile to destroy Smallville in one hour. He calls his friend Chloe, who is moving to the university, and asks her to leave the town that he wants to destroy because of the population of "meteor freaks." The army does not know which of the sixteen silos might have been broken in by Gabriel. Meanwhile, Clark and Lana sleep together in his room and early in the morning, Lana sneaks out of the house, but Jonathan and Martha see them. When Chloe calls Clark, he plots a simulation of a car accident with Chloe to force Gabriel to disclose his position. When Gabriel meets Chloe, Clark is deadly shot by the insane teenager, dying in the hospital. Suddenly, Lionel Luthor awakes from his catatonic situation in Belle Reve and Clark's body vanishes from the hospital which leads to both meeting at the Kryptonian Fortress of Solitude at the North Pole which leads to a surprising discovery for Clark. Elsewhere, the evil Lex continues to obsessively study the black spaceship at the LutherCorp warehouse and discovers that something else has climbed out of the ship.

Classmates from Lex and Oliver's reunion begin to die, and they begin to blame each other.