After attending the National Theatre School of Canada in Montreal, Oh had her breakthrou... gh in the 1993 CBC production of Runaway: The Diary of Evelyn Lau. Her portrayal of the title character, a 14-year-old runaway who endured hard times while living on the street, earned Oh a FIPA d'Or for Best Actress at Cannes. On the big screen, Oh first earned raves and recognition for her portrayal of a Chinese-Canadian woman struggling with both the demands of her conservative parents and those placed on her by society in response to her ethnic identity in Double Happiness. Her thoughtful, funny performance earned Oh her first Genie Award (Canada's equivalent of the Oscar), but unfortunately, further work was not immediately forthcoming.

Things began to look up when Oh was cast on the popular HBO series Arli$$ in 1996, and in a bit part in the hit comedy Bean (1997). Oh found greater success as one of the stars of Don McKellar's Last Night (1998), a comedy-drama about the end of the world that cast the actress as a woman trying to get across town in time to make good on a suicide pact she has with her husband (David Cronenberg). An internationally praised film that enjoyed a particularly strong reception at the Toronto and Cannes Festivals, it received a number of awards, including a second Genie for Oh. The following year, Oh took part in another critical hit with Audrey Wells' Guinevere, in which she appeared alongside fellow Canadian Sarah Polley as one of a number of young women taken under the wing of a dubious mentor (Stephen Rea). Oh ushered in the new millenium with a role in the largely-improvised ensemble film Dancing at the Blue Iguana, and the ensuing years saw the actress primarily take on a variety of small character roles in such films as Big Fat Liar and Under the Tuscan Sun. In 2004, however, she garnered a number of positive responses playing the impulsive-but-tough Stephanie in then-husband Alexander Payne's dramedy Sideways. The role would be a breakthrough, even if Payne and Oh announced the end of their marriage shortly after the film was honored at the 2005 Academy Awards. Oh's professional life continued to improve landing a major role on the television series Gray's Anatomy.

Her caustic, hilarious and often heartbreaking work in that series earned her strong reviews, as well as a Golden Globe Award and Emmy recognition. In 2006 she took time off from the show to appear opposite Robin Williams in the thriller The Night Listener.