He was 61.
Macdonald was diagnosed with cancer and battled the disease privately for nine years, according to Deadline.
Starting out as a comedian in his native Canada, Macdonald moved to the United States in the early 1990s and became a cast member on "Saturday Night Live." Macdonald was at his peak anchoring "Weekend Update," or "the fake news," a term Macdonald created nearly two decades before some other guy did. He had a habit of shocking viewers with his jokes, especially in regard to Michael Jackson's private life and the O.J. Simpson trial.
He was infamously fired from "SNL" in late 1997 by NBC boss Don Olhymer for apparently "not being funny." The fact that Olhymer was a close friend of Simpson had to have been a coincidence.
After his "SNL" exit, Macdonald did some movies, had a few sitcoms, and largely settled into being a full-time stand up comedian.
In 2018, Macdonald's comments about the #MeToo movement and fellow comedians Louis C.K. and Roseanne Barr led to the "The Tonight Show" canceling his appearance and spurred apologies from the comedian that could bring their own problems.
Macdonald's producing partner and friend Lori Jo Hoekstra said she was with him when he died.
"He was most proud of his comedy. He never wanted the diagnosis to affect the way the audience or any of his loved ones saw him. Norm was a pure comic. He once wrote that 'a joke should catch someone by surprise, it should never pander.' He certainly never pandered. Norm will be missed terribly," Hoekstra said in a statement.
He was scheduled to join the New York Comedy Festival lineup this November.
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The Associated Press contributed to this report.