Clark ends up in the Fortress of Solitude, where Jor-El tells him he must stay and ready himself in order to protect the Earth. When Chloe also finds herself in the Fortress, she must use Clark’s powers to keep from freezing to death.
Clark has his powers removed by Jor-El and, finally free of the outsider complex and the burden of superpowers, decides to dive headlong into a romance with Lana. When she, Jonathan and Martha are taken hostage, however, it’s up to him to save them all using only his wits and mortal abilities.
Chloe is informed by Gabriel that Smallville will be destroyed when he launches a missile upon the town. Clark tries to stop him, even though his superpowers are gone, and is fatally shot, with only Jor-El left to determine his ultimate fate. Meanwhile, Lex wants to explore the inside of the spaceship and thinks Lionel has the key that opens the craft.
During a beach party by a lake, Lois dives in and hits her head on her way into the water, but Clark is beaten to the punch when he tries to rescue her.
Lana hastily decides to enroll at Metropolis University, forcing her to scramble for housing. When she ends up moving into a sorority house, unbeknownst to her, one full of vampires, she is turned and instructed to go after Clark. Meanwhile, Chloe finds herself overwhelmed by the tough editor of the Daily Planet while applying for an internship.
An old friend of Jonathan's, Jake Jennings, comes by the farm hoping to drum up support for his Senate reelection bid, but things get harried when a woman is found murdered and later identified as Jake's stripper mistress. When Chloe coaxes Lois into posing as a stripper to get some answers about the murder, Lois is inadvertently kidnapped and intended to go up for sale on the slave market.
Clark comes to believe that everyone is scheming against him after exposure to silver kryptonite. When Chloe and the Kents scramble to help cure his delusional paranoia, Professor Fine comes into the picture with the solution, only his desire to help is more insidious than they realize.
Clark seeks Professor Fine's help when Martha contracts a mysterious illness which will kill her within hours, but the professor's advice to Clark is to tear down the Fortress of Solitude, convincing him that Jor-El is the cause of the disease.
Lex tries to decide whether or not to unearth information that will ruin Jonathan and Martha's lives to get a leg up in the senate election. When he is shot and left for dead during a mugging, he enters into a dream state in which his mother guides him through a life where he turned his back on wealth and power for happiness where he is married to a very-pregnant Lana.
After being threatened for his candidacy in the senate race, Jonathan is beaten severely and Clark hurries to discover the identity of the perpetrator, only to stumble upon a plot by Lex's devotees to get their man into office at any cost.
Lex and Lana are held captive in his mansion by two police officers who saw the spaceship landing and want Lex to give them the secret location at which he's been holding the ship.
Clark opens up to Lana about his love for her and the truth about his abilities as well as proposing to her. Jonathan wins the senate race, which sends Lex into a drunken tailspin.
After Martha is mugged and saved by a costumed vigilante, Clark tries to find her to get his father's stolen watch back . He and Chloe learn that the new "Daily Planet" reporter secretly doubles as the masked crusader and they team up to find the culprit.
Chloe experiences a possession from a dead girl whose body is buried somewhere inside the Talon, but while Chloe tries to find the one who murdered the girl, a concerned Clark and Lana try to find Chloe.
A young man turned into a cyborg for experimentation and held against his will by LutherCorp is let go by a kind doctor. Victor is hit by Lana while driving, but he escapes unscathed, prompting Clark to figure out who he is and why he was able to withstand the impact. Clark and Lana's efforts to help reunite Victor with his old life and girlfriend then hit a snag when Lex gets reinvolved and tries to kidnap Victor again.
Lex locates Professor Fine in Honduras and decides to pay him an ominous visit. Clark is intoxicated by a siren that has the ability to bend people to her will with the aid of a charm.
Lana ingests a dangerous liquid that allows her to come into contact with her deceased parents after despairing over the loss of her romance with Clark. Clark's efforts to help her end with him being injected with a different, and more potent kryptonite-based formula, inadvertently allowing him to see Jonathan. It is then that Clark learns that Lionel, who is now trying to get in tight with Martha, is aware of who Clark really is.
Clark and Martha take in a little girl whose mother was murdered, but the girl’s unique ability to shatter glass leads people to believe that she was the one responsible for her mother’s death. Meanwhile, Chloe is shocked when she walks in on an intimate situation between Lex and Lana.
Lionel is forced into a series of cat and mouse games by a shadowy, masked mastermind for the sake of his very survival. Martha's attempts to deal with Lionel about his knowledge of Clark's secret ends up putting her into the same twisted games as well.
Clark saves a stranger's life, only the man turns out to be a hitman with the ability to turn invisible. To express his gratitude, he buys Clark lavish gifts but when Clark rejects his offerings, he decides to kill Lex as his repayment. Clark catches Lana in the arms of Lex and realizes he's lost her for good. He must save Lex and Lana from the hitman after Lana stops his first attempt.
Clark is met by Jonathan's ghost while visiting his grave, who commands him to kill Lionel. Meanwhile, Lex devises a cure for Professor Fine's virus, only he becomes a victim of his own vaccine when Fine manages to outmaneuver him and inject it into him.
Lex's new powers that resulted from Fine's injection, come to full term. Lex reveals them to Lana who stands by him. Clark, Chloe and Lionel discover that Lex is meant to be the human vessel for Zod and Fine was preparing him to complete his plan as he unleashes the virus on Earth.