After graduating from high school, Durance moved to Vancouver, British Columbia, to pursue her interest in acting professionally. "I wanted to get my feet wet in a smaller area than Los Angeles when I gave it a try." Durance has said. She continued to study acting starting out with background work, graduating to commercials and then guest starring roles, landing more substantial roles each time.

In 2004, she guest-starred on The Chris Isaak Show, Tru Calling, Andromeda, Stargate SG-1, and The Collector.

However, she is perhaps best known for her role as Lois Lane on the WB series Smallville. She was a frequent guest-star for the fourth season of the show (2004-2005), and joined the regular cast for the fifth season (2005-2006).

She appeared on The Howard Stern Show in September of 2004, after she had already filmed a number of her first episodes on Smallville. When asked if her breasts were natural by Howard, she said "Yes", and he believed her and complimented her and said they were nice. Durance has never had plastic surgery of any kind.

She was listed as the highest new entrant and cover girl in "FHM"'s May 2006 issue including the World's 100 Sexiest Women at #38.