She started her acting career in 1974 as a cast member of The Second City in Toronto. In 1976, this theatre troupe created the television series SCTV, on which O'Hara became a regular performer. Memorable O'Hara characterizations on the show included Las Vegas scorcher (I wanna bear your children!) Lola Heatherton, buzzer-happy game show contestant Margaret Meehan, raunchy nightclub comedian Dusty Towne, soap opera seductress Sue Ellen and stage actress Sue Bopper Simpson.
In the late 1970s, she did various voice-overs for a number of cartoons, which would continue throughout her career. She was hired to replace Ann Risley when Saturday Night Live was being retooled in 1981 following Jean Doumanian's disastrous stint as executive producer. However, O'Hara quit the show without ever having made an appearance on it, primarily due to her shock after witnessing a long, loud diatribe by SNL writer Michael O'Donoghue. Her SNL position was then given to fellow Canadian Robin Duke, who had also replaced O'Hara for a season on SCTV.
Celebrities impersonated by O'Hara on SCTV include: Liv Ullmann, Katharine Hepburn, Diane Keaton, Joey Heatherton, Lola Falana, Elizabeth Taylor, Brooke Shields, Morgan Fairchild, Barbara Billingsley, Phyllis George, Charlotte Rampling, Monica Vitti, Jane Pauley, Rona Barrett, Tammy Faye Bakker, Angie Dickinson, Dorothy Kilgallen, Jessica Savitch, Linda Blair, Judith Crist, Rusty Warren, Gilda Radner, Joan Sutherland, Jane Fonda, Joan Embry,Candice Bergen, and Meryl Streep.
She had a role in The Last of the High Kings as a staunch Irish nationalist in 1970s Dublin. In 2006, O'Hara starred in her fourth Christopher Guest film, For Your Consideration (following Waiting for Guffman, Best in Show, and A Mighty Wind).
On June 9, 2007, she was inducted into the Canadian Walk of Fame.
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