Gary Lockwood was born in Van Nuys, California. He attended the University of California at Los Angeles on a football scholarship.

He began his career as a movie stuntman, and a stand-in for Anthony Perkins prior to his acting debut in 1959 in an uncredited bit role in Warlock. He also appeared as a police officer on in the Perry Mason. Two series came early in his career, ABC's Hawaii-set Follow the Sun in 1961-1962 cast him in as an adventurous magazine writer in Honolulu. In 1961, he appeared as a rodeo cowboy in love with an 18-year-old singer played by Tuesday Weld in ABC's Bus Stop. He then starred with Jeff Bridges in the Lloyd Bridges Show.

In 1964, he starred as a young U.S. Marine lieutenant in the NBC series The Lieutenant, and was produced by the Star Trek creator Gene Roddenberry, and The Man from U.N.C.L.E. creator Norman Felton.

He then starred in another NBC television series called The Kraft Mystery Theater opposite Sally Kellerman, with whom he would again appear in the second Star Trek pilot, "Where No Man Has Gone Before", as Gary Mitchell, and Kellerman as the ship's psychiatrist Dr. Elizabeth Dehner, who both develop super powers.

In 1966, he guest starred in "Reunion" of ABC's The Legend of Jesse James, starring Christopher Jones. and that same year, appeared as Danny Hamil on the episode "Day of Thunder" of NBC's drama, The Long Hot Summer, based loosely on the works of William Faulkner, as well as Hein the two-part episode "The Raid" of CBS's Gunsmoke with James Arness.

He co-starred with Stefanie Powers (his wife at the time) in an episode of ABC's Love, American Style.

In 1968 he was cast as the co-star in director Stanley Kubrick's legendary Sci-Fi film 2001:A Space Odyssey, starring as Dr. Frank Poole.

In 1983 he made a guest starring role in the series Hart to Hart starring Robert Wagner, and [now his ex-wife] Stefanie Powers.

Between 1959 and 2004, he had roles in some forty theatrical and made-for-TV features and made almost eighty TV guest appearances, including several as a villain on CBS-TV's Barnaby Jones starring Buddy Ebsen.