Devane was born in Albany, New York to Joe Devane, who worked as Franklin D. Roosevelt's chauffeur when he was Governor of New York. Devane graduated from the American Academy of Dramatic Arts in New York.

Devane is perhaps most widely recognized for his ten years as the villainous Greg Sumner on the drama series Knots Landing, and his role as President Kennedy in the TV film The Missiles of October, about the Cuban Missile Crisis. Devane has also appeared in such films as McCabe & Mrs. Miller (1971), Family Plot (1976), Marathon Man (1976), Rolling Thunder (1977), The Bad News Bears in Breaking Training (1977), Testament (1983) and Space Cowboys (2000).

He recently appeared on two different evening dramas as members of the United States Cabinet. In 2004, he guest-starred as United States Secretary of State and potential vice-presidential nominee Lewis Berryhill on The West Wing. In 2005, he joined the cast of 24 as United States Secretary of Defense James Heller in the show's fourth season. During the middle of the season, however, Devane was one of several cast members to be written out of the series. He returned for one more episode later that season, and again in the show's fifth season (2006). In his role on The West Wing, Devane appeared in several scenes with the show's fictional President Josiah Bartlet, played by Martin Sheen. Devane and Sheen also appeared together as President Kennedy and his brother Robert F. Kennedy, respectively, 30 years earlier in The Missiles of October.

In 2004, Devane also starred in three episodes of Stargate SG-1, as President Hayes. Most recently he starred in the short-lived ABC sitcom, Crumbs.