Born in Quebec City, Quebec, MacDonald became a stand up comedian, performing in comedy clubs across Canada. MacDonald eventually moved to Los Angeles, California, and became a writer for the popular Roseanne television series.
MacDonald joined the cast of NBC's popular Saturday Night Live program in 1993, where he hosted the "Weekend Update" segment, and occasionally did impressions of Larry King, Burt Reynolds, David Letterman, Bob Dole and others. MacDonald was fired from the show in 1998 by NBC executive Don Ohlmeyer, who apparently was of the opinion that MacDonald was simply "not funny". Some reports suggested that the show's creator and fellow Canadian, Lorne Michaels was also involved in the decision, but both MacDonald and Michaels have denied this. Some have speculated that MacDonald was fired because of his frequent jokes on the show about O. J. Simpson, who happens to be a good friend of Ohlmeyer's.
Soon after, MacDonald starred in his first movie entitled Dirty Work, which was released to theaters in 1998. The film featured performances from veteran actors and comedians like Jack Warden, Don Rickles, Chevy Chase, Chris Farley, and Adam Sandler. Later that year, MacDonald would also lend his voice to one of the animals in the Eddie Murphy remake of Dr. Dolittle.
In 1999, MacDonald starred in a sitcom called The Norm Show, which lasted three seasons on the ABC television network. Also that year, MacDonald portrayed Michael Richards in the movie, Man On The Moon, which was the story of comedian Andy Kaufman's short and unusual life.
MacDonald returned to Saturday Night Live to host the October 23, 1999 show. In his somewhat notorious opening monologue, he expressed resentment at having been fired, and says that since he left the show had "gotten really bad". This comment received a mixed reaction from the audience.
MacDonald starred in his second motion picture in 2000, entitled Screwed.
MacDonald is currently starring in "A Minute With Stan Hooper"
MacDonald's brothers Neil and Leslie are both newscasters for the Canadian Broadcasting Corporation.