Clark Kent now carries a full load of classes at Central Kansas University, but that's not all he carries. He carries the full weight of his - perhaps the world's - destiny. In season five, Clark finally begins to accept his destiny and takes giant leaps towards becoming the Man of Steel. He also cross path with professor Milton Fine, whose presence in Smallville will have a devastating effect on his already deteriorating friendship with Lex.
Lana greets two new Kryptonian arrivals from the ship, Nam-Ek and Aethyr, and their presence poses a grave danger to Clark and his family & friends.
Clark faces off against three Belle Reve prisoners who plan to force him to help break into the sanitarium's mysterious "Level Three."
A krypto-mutant, Gabriel, hacks into missile codes and prepares to eliminate krypto-mutants in Smallville once and for all. A powerless Clark confronts him and is shot, and only Jor-El can save him.
At a party at Crater Lake, Lois is saved from drowning by Arthur "A.C." Curry. Arthur has incredible swimming abilities, but also a secret agenda aimed at...Lex. Meanwhile, Professor Fine discussed Lex's weapons-manfucturing operations with Clark.
Lana joins a sorority to get housing for her last-minute college registration, but the sisters have a deadly agenda which involves turning Lana into a vampire like themselves and sending her against Clark. Meanwhile, Chloe applies to become an intern at the Daily Planet and runs up against the editor-in-chief, Pauline Kahn.
Jonathan's oldest friend, Senator Jack Jennings, comes to Smallville looking for support in his re-election campaign, but is framed for the murder of his mistress, requiring Lois to go undercover as a stripper.
Clark gives into paranoid delusions brought on by exposure to new "silver" kryptonite, and Professor Fine is the only one who can save him... before he kills Lana.
When Martha comes down with a strange disease, Professor Fine convinces Clark that Jor-El is responsible and that the Fortress must be trying to eliminate the father of Kal-El. But Professor Fine has an ulterior motive which comes to fruition when they arrive.
Lex considers whether to turn an operative loose to obtain or fake damaging information against Jonathan to upset his Senatorial race. But when Lex is shot, he falls into a coma and is visited by the ghost of his mother, who shows him what his life could be like if he frees himself from his father. Meanwhile, Clark helps deliver Christmas presents.
The Senatorial race between Jonathan and Lex heats up when Jonathan receives an anonymous threat warning him to drop out of the election. When Clark finds Jonathan badly beaten he determines to find the attackers. Lois is thrown into the mix when she is captured and she is forced to assassinate Jonathan during his speech.
Lex and Lana are at the mercy of a deranged Smallville deputy who plans to keep them captive until Lex reveals the location of the Kryptonian spaceship. Meanwhile, the Kents can't see eye-to-eye on campaign financing.
Clark reveals his secret to Lana, Jonathan and Lex learn the results of the senatorial election, and there is a tragic car accident on the highway that takes the life of someone Clark loves, forcing Clark to appeal to Jor-El for help.
Clark discovers that the new assistant at the Daily Planet, a bespectacled, bumbling woman named Andrea, is actually a mysterious female vigilante who stalks Suicide Slum. Her path crosses Clark's as they both seek the same criminal. Meanwhile, Clark's bottled-up grief threatens to get the best of him and LuthorCorp experiences a shakeup.
Chloe is possessed by the spirit of a young girl whose body is sealed in the Talon's walls, and goes searching for the girl's killer while Clark and Lois try to track her down.
Clark finds himself up against Lex when he befriends Victor Stone, a half-machine, half-human subject who escapes from LuthorCorp with the aid of a sympathetic doctor.
Clark is hypnotized by a woman who uses a supposedly magical charm to control others - he reveals his super powers and is sent to kill Lex. Meanwhile, Lex has tracked down the missing Professor Fine and plans to confront him, unaware that Clark is coming to murder him.
Distraught over her break-up with Clark, Lana goes to a rogue medical student who experiments with a dangerous kryptonite-based serum that allows people to flat-line but see their dead loved ones. Lana attempts to see her dead parents using the serum and when Clark returns from Honduras to help her, the doctor injects him with the serum and Clark speaks with his dead father...who warns him that Lionel knows his secret. Meanwhile, Lionel continues working to get closer to Martha, and Lex has a near-death vision of his mother.
Clark befriends a little girl who has the ability to telekinetically shatter glass, then comes to her aid when it's believed she killed her mother in a brutal stabbing attack. Meanwhile Lex and Lana grow closer together and Chloe finds out about it.
Lionel is taken hostage by a masked man who forces him to play elaborate games for the prize of staying alive. Martha goes to confront Lionel after Clark tells her Lionel knows his secret and becomes a part of the game herself, fighting for her life.
Clark saves a man who in gratitude decides to help Clark in return...by using his ability to turn invisible and his skill as a hitman to kill Lex so Clark can reunite with Lana. And Clark and Lana finally square off about Lana's new relationship.
Clark and Martha are both visited by Jonathan's ghost, who warns them about Lionel and claims that Clark must kill him to stop him. Meanwhile Fine will do whatever it takes to get the vaccine from Lex.