[2] Durance moved to Vancouver in 1999 to pursue her interest in acting professionally and study at the Yaletown Actors Lab.

[2] She has guest-starred in television series, including Andromeda, Stargate SG-1, Charlie's Angels, Harry's Law and Private Eyes.

[5][6] In 2004, Durance was cast in her breakout role as Lois Lane on the television series Smallville.

[13] In 2012, Durance began starring in the lead role in the CTV medical drama television series Saving Hope, as Chief Surgical Dr. Alex Reid.

[16] In season 3, Durance's real-life pregnancy was worked into her character Alex Reid and the series.

[16][17] Durance appeared in the television series Supergirl in a recurring role as Kara's Kryptonian mother, Alura Zor-El.

[18][19] In 2019, Durance and her Smallville co-star Tom Welling reprised their roles as Lois and Clark in the Batwoman episode of the Arrowverse crossover event "Crisis on Infinite Earths".

[25] In August 2006, she co-hosted the Superman/Batman #26 art auction with Jeph Loeb at the Wizard World Chicago convention.