Clark returns to Smallville re-programmed as Kal-El. Intent on fulfilling his destiny, Kal-El takes to the skies to steal a powerful Kryptonian crystal. Determined to save her son, Martha turns to Dr. Swann's emissary, Bridgette Crosby, and learns about a surprising new form of kryptonite. Meanwhile, Lois Lane comes to town to investigate the murder of her cousin Chloe. Also, Lana returns from Paris with a new attitude and a new boyfriend, Jonathan lies in a coma, and Lionel faces a grim new life in prison.
Clark and Lois Lane investigate Chloe's apparent murder, but are stopped by an army officer, General Sam Lane, who turns out to be Lois' father. Lois suspects that Sam knows more about Chloe's death than he will admit, and Clark discovers that Sam has recently been in contact with Lex. Jason arrives from Paris and convinces Lana to continue their relationship. Suspecting that Chloe is still alive, Lionel sends an assassin with the power to morph his limbs into metallic weapons to keep Chloe from testifying against him.
Clark faces a surprising new foe in the form of a shy high school girl who turns to plastic surgery to enhance her looks and boost her popularity. However, things go awry when she discovers that her kryptonite-enhanced beauty causes harm to anyone she kisses - and she decides her next victim will be Lana. Meanwhile, Jason and Lana continue to hide their relationship from Clark.
Clark joins the football team at school and is immediately given the starting quarterback position after the old quarterback starts a fight with new coach Jason. Curious about the behavior change in his old teammate, Clark and Lois investigate and discover that the cheerleaders are poisoning the teams' water with kryptonite, turning the players into Stepford-like boyfriends.
After Jonathan's wallet is stolen, Clark superspeeds after the thief but is stunned when he cannot catch him. The thief, Bart, a.k.a. The Flash, later shows up at the farm and tries to talk Clark into leaving Smallville for a life on the road together, flexing their super powers. Meanwhile, Lex buys a priceless framed manuscript with Kryptonian symbols and Clark learns that it contains a mysterious hidden map. However, when Bart steals the manuscript from Lex, he inadvertently puts Clark's life in danger and must make the decision whether to save Clark or himself.
Clark hears a painful ringing sound in his ears and is drawn to the prison where Lionel is being held. When he sees Lionel attempt to stab Lex with a strange glowing stone, Clark grabs for the stone causing the two men to switch bodies. Learning his new body has super powers, Lionel immediately begins wreaking havoc on Smallville. Trapped behind bars without his powers, Clark must figure out a way to get his body and powers back in order to save his friends and family.
Chloe is drawn into an underground gambling ring at school run by foreign exchange student Mikhail Mxyzptlk and loses her savings on a football game after Mxyzptlk uses his powers to control all the players - including Clark. When Chloe discovers Mxyzptlk's secret, he kidnaps her and threatens to kill her unless Clark throws the championship game. Meanwhile, Lex threatens Mxyzptlk with deportation unless he uses his powers for Lex's benefit.
After Lana reads from a spell book written in the 1600s, she, Lois, and Chloe become possessed by witches that had been burned at the stake. The three witches have come back to seek revenge and search for the powerful Kryptonian crystals, wreaking havoc on the town in the process. Clark attempts to stop the witches but they strip him of his powers and force him to reveal the location of the crystal he hid in the cave.
After Lex is accused of killing a young woman, Clark sets out to prove his innocence and turns to an unlikely source for help - Lionel. Swearing he is a changed man, Lionel offers Clark insight into the crime but he asks for something in return. Meanwhile, Lana meets Jason's parents and has a vivid flashback of the incident in Paris, leading her to suspect that Jason's mother was there when she got her tattoo.
Lex's secret experiment at Luthorcorp goes awry and causes a dangerous toxin to be released into Smallville. Those infected by the toxin, including Clark, Lana, Lex, and Jason, imagine their greatest fears come true and then fall into a coma. Desperate to find a cure, Clark gives some of his blood to Lex and is stunned at what Lex does with the antidote.
Claiming to be cured, Alicia is released from Belle Reve hospital and comes to Smallville to rekindle her relationship with Clark. Initially skeptical of Alicia, Clark finds himself enjoying a relationship with someone who knows his secret, but when she pushes for more he hesitiates, causing her to use red kryptonite on him. "Bad Clark" emerges and whisks Alicia off to get married in Las Vegas. Meanwhile, Lana decides to have sex with Jason in order to win him back.
Clark has big concerns after his new girlfriend Alicia becomes the prime suspect in a brutal attack against Lana and Jason. Clark initially defends Alicia, but when the evidence begins to pile up he is forced to take a hard truthful look at the situation. Hurt by Clark's actions, Alicia forces Clark to unknowingly reveal his powers in front of Chloe. Meanwhile, Jason's mother returns to town with an offer for Lex.
In an effort to recruit Clark for their football team, Met U sends their star player Geoff to show Clark the perks of attending Met U. However, after one of Met U's players dies under mysterious circumstances and Lois is arrested for his murder, Clark discovers that Geoff has super powers and is using them to paralyze anyone who gets in his way, including Lois. Meanwhile, Chloe continues to watch Clark to learn more about his secret.
While driving, Lois accidentally hits a dog and she brings it back to the farm to heal. Clark realizes this is no ordinary dog after the pup lifts up a car to retrieve a ball. Clark and Lois learn the dog is a product of an aborted LuthorCorp experiment and is being used to commit crimes, but when Lois is kidnapped by the robbers and Clark is weakened by kryptonite, it is up to the dog to save them. Meanwhile, Lana questions Jason's involvement in his mother's schemes.
After learning that Jason and Lex are in China searching for one of the mysterious kryptonian crystals, Clark and Lana follow in the hopes of finding it first. Clark finds an artifact that leads them to the crystal but he must battle Isobel, the witch, who has once again inhabited Lana's body in order to take the crystal for herself. Meanwhile, Lex has more information on the crystals than he is letting on.
Lois's younger sister, Lucy, with whom Lois doesn't get along, comes to town and charms everyone she meets. However, Clark discovers a darker side to Lucy after he catches her stealing money from the Talon and forces her to reveal the truth about her sudden appearance in Smallville, a truth that puts Lois in grave danger. Meanwhile, the crystal disappears from Lana's apartment and Jason accuses Lionel of stealing it.
A glimpse of the future Lex Luthor is revealed after a kryptonite explosion splits Lex in two and his evil side - Alexander - is released. Alexander immediately imprisons Lex in the mansion and begins his rampage by trying to kill Clark and Chloe in the lab, jousting with Lionel and convincing him to return to the dark side, and finally, threatening to close the Talon unless Lana moves in with him.
A stunned Chloe is nominated for Prom Queen and tries to talk a reluctant Clark and Lana into attending the dance with her. However, after her rival Dawn, a wannabe Prom queen, crashes her car into a ravine filled with kryptonite, Dawn's spirit is released and she enters the bodies of the others making them act out of character. As a result, Lana asks Clark to be her date, Lois attends the Prom, and Chloe sets the school on fire. Lex gives the seniors a special gift by having the band Lifehouse play at the dance.
Kevin, a boy who can cause people to temporarily lose their memory, turns his powers on Clark and causes him to have total amnesia. Chloe discovers what has happened and must teach Clark about his superpowers while simultaneously trying to keep him from accidentally revealing them to others. On his trip down memory lane, Clark meets Lana, falls in love all over again, and decides to share his secret with her. Lex takes advantage of the situation and convinces Clark to show him where the three stones are hidden.
Clark and Lana discover an abandoned baby in the cornfield and take him back to the Kent farm. However, once the baby ages from a newborn to a 7-year-old in a matter of days, the two realize he is aging at a rapid rate and frantically search for a cure before the disease kills him. Meanwhile, Genevieve orders Lionel to kill Lana or else she will send him back to prison.
Clark must stop the school photographer after he sets up a secret simulated high school and begins kidnapping students - starting with Chloe - to keep the glory days of high school going forever. Lex and Lionel are kidnapped and tortured by the Teagues in an effort to find the crystal. However, after Genevieve realizes Lana has it, she decides to put an end to the hunt once and for all.
Clark begins to piece together the reason he was sent to Earth after he has a nightmare that something horrible is going to happen to Smallville and heads to the cave to seek answers from Jor-El. His biological father tells him he must reunite the three crystals immediately or a disaster of epic proportions will befall the planet and even Clark won't be able to stop it. Meanwhile, Lex helps Lana escape Smallville after the death of Genevieve Teague, then takes shocking action to get one of the crystals away from Lionel. Realizing they are connected to Clark, Chloe tries to stop Lex from discovering the truth about the crystals. Jason takes Jonathan and Martha hostage and threatens to kill Martha unless Jonathan tells him where Clark hid the crystals.