In the late 1970s, she provided voice-overs for a number of cartoons, work which would continue throughout her career. During a short time in the early 1980s when SCTV was in between network deals, she was hired to replace Ann Risley when Saturday Night Live was being retooled in 1981. However, she quit the show without ever appearing on air, choosing to go back to SCTV when the show signed on with NBC. Her SNL position was then given to fellow Canadian Robin Duke, who had also replaced O’Hara for a season on SCTV.
O’Hara began her career on television, apart from SCTV, in the mid-1970s. She appeared in the 1976 television film The Rimshots, the children’s television series Coming Up Rosie for a year, and television specials, such as Witch’s Night Out and Intergalactic Thanksgiving. But it was her performances on SCTV that earned her fame in Canada, which is why she returned to the show, not only as an actress but as a writer for both SCTVand SCTV Network 90, which earned her an Emmy Award for outstanding writing and two Emmy Award nominations. She also has written for SCTV Channel.
O’Hara has appeared in a number of television series and television films and continues to work in television. During the ’90s, she made guest appearances on Tales from the Crypt, Oh Baby, Morton & Hayes and The Larry Sanders Show. She served as actress and director on Dream On and The Outer Limits, the revival of the ’60s series of the same name. In the past decade, O’Hara has guest-starred on top-rated television series including Six Feet Under and Curb Your Enthusiasm. In May 2008, it was announced that she had signed on to star in the upcoming ABC dramedy Good Behavior. Her role in the 2010 television film Temple Grandin earned her three award nominations: a Primetime Emmy Award, a Satellite Award, and a Screen Actors Guild Award.
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, including Martin Scorsese’s After Hours and Heartburn, with Meryl Streep. She had more notable roles in Beetlejuice, the blockbuster hit Home Alone and its sequel Home Alone 2: Lost in New York. In 1992, O’Hara worked alongside Jeff Daniels in the comedy There Goes the Neighborhood. O’Hara continued to appear in many films during the 1990s and the beginning of the 21st century. She received roles in four of Christopher Guest’s mockumentary films, three of which earned her awards and nominations: Waiting for Guffman, Best in Show, A Mighty Wind and For Your Consideration. Her role in 1999’s The Life Before This won her a Genie Award for Best Performance by an Actress in a Supporting Role. She also appeared in episodes 6, 10 and 11 on the tenth and final series of the UK Whose Line Is It Anyway? In 2006, she starred with Christina Ricci in the fantasy feature Penelope. O’Hara has served as a voice artist in a number of animated movies, including The Nightmare Before Christmas, Chicken Little, Over the Hedge, Monster House, Brother Bear 2 and Frankenweenie.
On June 9, 2007, O’Hara was inducted into Canada’s Walk of Fame. On February 28, 2010, she spoke at the Closing Ceremonies of the Vancouver 2010 Winter Olympics. In 2015 Canada Post placed her image on a postage stamp.
For her funny-faced and funny-voiced turn on Schitt’s Creek—as former soap opera actress Moira Rose Her role has earned her two Canadian Screen Awards for Best Lead Actress in a Comedy Series, at the 4th Canadian Screen Awards in 2016 and the 5th Canadian Screen Awards in 2017.