Catherine Anne O'Hara enrolled at Burnhamthorpe Collegiate Institute. Catherine started her comedy career in 1974 as a cast member of The Second City in her native Toronto. Two years later, this theater troupe created the sketch comedy show SCTV, for which O'Hara became a regular performer. Her memorable characterizations on the show included Las Vegas scorcher 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.
O'Hara has also had a successful career in film. She made her feature debut in the 1980 film Double Negative, which also starred her SCTV co-stars John Candy, Eugene Levy, and Joe Flaherty. Throughout the 1980s and 1990s, O'Hara appeared in many supporting roles. Notable films roles include the over-dramatic and self-centered Delia Deetz in Tim Burton's Beetlejuice (1988), Kate McCallister, Macaulay Culkin's on-screen mother in Home Alone (1990) and its sequel Home Alone 2: Lost in New York (1992).
In the late 1970s, she provided voice-overs for a number of cartoons, work which would continue throughout her career.
For her contribution, the Canada post released a postage stamp of her in 2015.