Jensen Ackles, who played Jason Teague, later became better known to DC fans as another Jason. He also made a name for himself as Dean Winchester on Supernatural just a year after his appearance here. In fact, that's the role he actually left Smallville for.
Meghan Ory, now well-known for her role as Red Riding Hood on Once Upon a Time, played a cheerleader who was almost killed in a season three episode.
Serinda Swan famously played Zatanna on Smallville, and went on to play Paige on USA Network's Graceland, along with her co-star Brandon McLaren, who played two small roles on Smallville (first as a deliveryman in "Covenant" and then the unfortunate victim of Phantom Zone criminal Baern in "Fallout") before being cast on Graceland as Jakes. In fact, his role in “Covenant” may very well have been one of his last North American roles before getting the part of Jack Landors, the Red Ranger of Power Rangers S.P.D.. Swan also played queen Medusa in the short-lived Inhumans series.
Joe Morton, later known for his roles in Eureka and Scandal appeared in the first two seasons as Professor Hamilton.
Dave Bautista plays yet another super-strong alien in the episode 'Static'
A young Jessica Parker Kennedy plays metahuman Plastique in several episodes, several years before playing another DC metahuman on The Flash (2014) as Barry's speedster daughter from the future. She is also now known for her role on Black Sails.
Lizzy Caplan had a recurring role as meteor freak Tina Greer, who was obsessed with Lana. She would later be known widely for her roles on Mean Girls and Masters of Sex.
Adam Brody appeared as a meteor freak in the first season. He became more known for his roles on Gilmore Girls and The O.C.. Brody also played the grown-up hero version of Freddy Freeman in SHAZAM! (2019) and its sequel.
would also be slightly better off heralding a different 'superman'.