The first episode tells the story of the meteor shower that hit Smallville and changed life in the Kansas town forever. Clark Kent meets Lex Luthor for the first time and encounters the first in a long line of humans mutated by the strange green meteor rocks that accompanied him on his journey to Earth.

Clark must deal with Greg, a nerdish bug collector with a crush on Lana who gains the ability of various insects and uses them to lash out at anyone who opposes him.

Former Smallville High cartoonist Justin returns to Smallville after he loses the use of his hands in a hit and run accident. Meanwhile, Lex's former nanny, Pamela, comes back to see how he's doing and to apologize for leaving him after his mother's death, bringing up some old issues for Lex.

Clark travels to New York to meet Dr. Swann, a brilliant scientist who holds a message for Clark from his home planet. Meanwhile Lana decides to move out of Chloe's house after they get into an argument about Clark.

A sense of foreboding surrounds Smallville as Clark must choose between staying with Lana and his family or fulfilling his destiny to rule the Earth. Lex and Helen prepare for their marriage, and Chloe considers Lionel's offer to investigate Clark.

Under the influence of red kryptonite, Clark is following a life of crime in Metropolis while his friends and parents desperately try to find him. Lex is forced to confront his personal demons on a desert island, while Lionel holds a funeral for his presumed-dead son. And Jonathan Kent must pay a high price for the power necessary to bring his son back home.

Believing that key information about his father's past was lost when his memory was erased, Lex decides to join an experimental program with Dr. Garner to regain the information so he can turn his father over to the FBI. Knowing that Lex will discover his secret if he regains his memory, Clark tries to stop him but is caught by Lionel and the doctor and exposed to the same radical treatment so that Lionel can solve the mystery of Clark's past.

Clark returns to Smallville as Kal-El - intent on fulfilling his destiny, he goes after a powerful kryptonian crystal that Lex has obtained in Egypt. Meanwhile, newcomer Lois Lane arrives in Smallville to look into the death of her cousin Chloe, and Lana returns from Paris with a new boyfriend. Jonathan lies in a coma after the events of last year's season finale and Lionel must deal with his new life in prison.