McCormack grew up in Calgary. As the son of an actor, he visited with the support of his parents theater school at the Canadian Ryerson University and the Banff Centre for the Arts. He then played five seasons with the Stratford Festival Theatre.
A wide audience McCormack is best known for the title role of Will Truman in the American sitcom Will & Grace. For his role as Will, he was nominated five times for a Golden Globe and won once, in 2001, an Emmy. After several guest appearances and supporting roles in several films and series, he takes over since 2012 in the crime drama Perception the lead role of Dr. Daniel Pierce.
Since August 3, 1997 he is married to Janet Holden. The two have a son. McCormack now owns next to the Canadian and the U.S. citizenship.