The series recounts the early adventures of Kryptonian Clark Kent as he adjusts to life in the fictional town of Smallville, Kansas, during the years before he becomes Superman.

Regular cast members during season six include Tom Welling, Kristin Kreuk, Michael Rosenbaum, Erica Durance, Allison Mack, John Glover, and Annette O'Toole.

Season six key story arcs involve Clark (Welling) trying to recapture several escaped criminals from the Phantom Zone, the destinies of Lionel (Glover) and Lex (Rosenbaum) following the aftermath of Lex's possession by Zod and Lionel's adoption as the emissary of Jor-El, and the introductions of DC Comics characters Jimmy Olsen, Oliver Queen and Martian Manhunter, played by Aaron Ashmore, Justin Hartley, and Phil Morris respectively.

According to Lisa Gregorian, Executive Vice President of worldwide marketing at Warner Bros. Television Group, these promotional tie-ins were ways to get fans more connected to the show.

The online series allowed viewers to investigate alongside the fictional team, in an effort to win prizes.

[33] The VES recognized the season in 2008, nominating "Justice" for Outstanding Compositing in a Broadcast Program or Commercial.

[35][36] David Moxness won the American Society of Cinematographers Outstanding Achievement in Cinematography Award for his work on "Arrow".