Rothery knew that she belonged in front of the camera when she played in the CBC Halloween special, Boo, at the age of eighteen. She is best known for her starring role of Dr. Janet Fraiser on Stargate SG-1, which she played from the show's beginning in 1997 through 2004 (and again as a guest appearance in 2006).

Rothery has appeared in many other sci-fi series, including The X-Files, The Outer Limits, First Wave, Stargate SG-1, Jeremiah, M.A.N.T.I.S., Kyle XY, Eureka, and many others. She played a small role in the Babylon 5 direct-to-DVD movie, Voices in the Dark, as ISN Reporter, Ms. Chambers. She played Lenore Molee in the 1994 TV movie, For the Love of Nancy, and has also done voice acting work. In 2010, she was on the Battlestar Galactica prequel, Caprica, as Evelyn (the mother of Battlestar Galactica's Admiral William Adama). Her most recent work has been her role in A Fairly Odd Movie: Grow Up, Timmy Turner!, where she plays Mrs. Turner (Timmy Turner's mom). The movie premiered July 9, 2011, at 8 pm (ET/PT), on Nickelodeon.

Most recently, Rothery has been acting in theater in her native Vancouver — appearing in Kiss Me, Kate and The Taming of the Shrew in March 2006. In March 2007 she appeared in A Delicate Balance, a play by Edward Albee, for which she was nominated for a Jessie Richardson Theatre Award.

Rothery starred in the Canadian premiere of Good Boys and True, written by Roberto Aguirre-Sacasa, and directed by Jeff Hyslop. The play ran at the Firehall Arts Centre in Vancouver in 2009.

Rothery has been nominated for four Leo Awards. In 2004 she was nominated in two categories: Best Supporting Performance by a Female in a Dramatic Series for the Stargate SG-1 episode "Lifeboat," and Best Guest Performance by a Female in a Dramatic Series on The Collector. In 2008 she was nominated in the category: Best Performance by a Female in a Short Drama for her work in the short film Coffee Diva. In 2009 she was nominated in the category: Best Supporting Performance by a Female in a Dramatic Series for the episode "Sound of Loneliness" from The Guard.