Born and raised in Toronto, McCormack began acting in high school and continued during his college years at the Ryerson Theatre School. He spent the next seven years working in Canadian theater, including five seasons with the Stratford Festival, where he appeared in A Midsummer Night's Dream, Henry V, Murder in the Cathedral and Three Sisters. He also performed with the Manitoba Theatre Centre in Burn This and at Toronto's Royal Alexandra Theatre in Biloxi Blues.
On television, McCormack spent two years as the dashing Colonel Mosby on the series Lonesome Dove: The Outlaw Years, and he has appeared as a guest star on Ally McBeal and Veronica's Closet. McCormack landed the role of Will Truman in the successful eight-year run of Will & Grace, for which he won his first Emmy for Outstanding Lead Actor in a Comedy Series in November 4, 2001. McCormack and his wife divide their time between their permanent home in Los Angeles and a second home in Vancouver.