McGavin began his career working as a set painter for Columbia Pictures. In 1954, he originated roles in Broadway productions of My Three Angels and The Rainmaker, followed by roles in David Lean's Summertime and Otto Preminger's The Man with the Golden Arm (both 1955).
On television, McGavin portrayed the title character in Mickey Spillane's Mike Hammer (1958–1959), as well as starred in Riverboat (1959–1961) and Kolchak: The Night Stalker (1974–1975). For his recurring role on the sitcom Murphy Brown, he received a nomination for the Primetime Emmy Award for Outstanding Guest Actor in a Comedy Series.
His film credits include Airport '77 (1977), Hot Lead and Cold Feet (1978), A Christmas Story (1983), Happy Hell Night (1992), and Billy Madison (1995). Despite playing a significant role in the baseball film The Natural (1984), due to a contract dispute, McGavin was uncredited for his portrayal as shady bookie, Gus Sands.

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