He entered the world of comedy by performing stand-up acts at Ottawa clubs and then started performing all over Canada as his confidence grew. In 1987 he got a chance to perform at the ‘Just For Laughs’ Comedy Festival.
Realizing that he needed to be on a bigger platform to further his career, he went to Los Angeles in order to try his luck. There he found work as a writer for the sitcom ‘Roseanne’.
In 1993, he joined NBC’s ‘Saturday Night Live’ (SNL) television program as a writer and a cast member. There he performed impersonations of different celebrities like Larry King, David Letterman, and Burt Reynolds which had the audience rolling in laughter.
He was made the anchor of the segment ‘Weekend Update’, a fake news section of the SNL after the departure of the previous host Kevin Nealon. As an anchor he often made references to topics like prison rapes, crack whores, etc. He often made scathing remarks about celebrities like Michael Jackson and Marion Barry.
He was fired from SNL in late 1997 as the anchor of the ‘Weekend Update’, ostensibly the reason being that MacDonald was “not funny”. However, it is widely believed that some tensions had been brewing between him and the management which resulted in his being fired.
He made the last of his appearances on SNL in 1998. He appeared as the host of a fictitious TV show called ‘Who’s More Grizzled?’ and asked questions to the host and the guest played by Garth Brooks and Robert Duvall, respectively.
After being kicked out of SNL, he starred in the comedy buddy film ‘Dirty Work’, in 1998. The plot revolved around a group of friends who start a revenge-for-hire business. The film became a cult classic in spite of getting negative reviews.
In 1998, he voiced the character of Lucky the dog in the remake of ‘Dr.Dolittle’ starring Eddie Murphy. He reprised the role in the sequels ‘Dr.Dolittle 2’ (2001) and ‘Dr.Dolittle 3’ (2006).
He played Norm Henderson on the television sitcom ‘The Norm Show’ that ran from 1999 through 2001 on ABC network. The show focused on the life of a former NHL hockey player who faces a life ban because of gambling and tax evasion.
He appeared on the Celebrity Edition of ‘Who Wants to Be a Millionaire?’ in November 2000 and won $500,000 fro Paul Newman’s Charity Camp.
In 2003, he appeared as Stan Hooper in the sitcom ‘A Minute with Stan Hooper’ in which he played the ‘straight man’ among a cast of eccentric characters. The show, however, was not a success and had to be cancelled after one season.
He voiced Norm the Genie in ‘The Fairly Odd Parents’ (2004-05), Join Twosomes Penguin in ‘Farce of the Penguins’ in 2006 and ‘Buster the Fox’ in ‘Christmas is Here Again’ in 2007.
He was a frequent guest on ‘The Tonight Show with Conan O’Brien’ during 2009 and 2010. He made appearances on the show during its initial as well as final episodes. His performances became the highlight of the show.
He has appeared in four episodes of the sitcom ‘The Middle’ as Rusty Heck starting from 2010. The story revolves around the lives of a Midwestern woman, her husband, and three children.