Hopkins appeared in more than 100 film and television roles in a career of more than 40 years, including the major studio films The Wild Bunch (1969), The Bridge at Remagen (1969), The Getaway (1972), American Graffiti (1973), The Man Who Loved Cat Dancing (1973), The Killer Elite (1975), Posse (1975), A Small Town in Texas (1976), Midnight Express (1978), and More American Graffiti (1979). His final film, Hillbilly Elegy, was directed by his long-time friend Ron Howard and released in 2020.
After Hopkins' first roles in major films in the early 1970s he appeared in White Lightning (1973). Hopkins played Roy Boone. Jerry Reed and Hopkins played brothers Joe Hawkins and Tom Hawkins in the 1985 film What Comes Around.
Hopkins starred or co-starred in many made-for-television movies of the mid-1970s, including Gondola (1973), Judgment: The Court Martial of Lieutenant William Calley (1975), The Runaway Barge (1975), The Kansas City Massacre (1975), The Invasion of Johnson County (1976), Dawn: Portrait of a Teenage Runaway (1976), Woman on the Run (1977), Thaddeus Rose and Eddie (1978), Crisis in Sun Valley (1978), and The Busters (1978).

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