He also played Lewis Morris of New York in the musical film 1776 and Everett Scovill, a thinly disguised portrait of Charles Manson's attorney Irving Kanarek, in the television movie Helter Skelter.

[citation needed] Caine appeared on Broadway in Wonderful Town, Inherit the Wind, Lunatics and Lovers, and Tiger at the Gates.

He was featured in such films as From the Terrace (1960), Pay or Die (1960), as the husband of the character portrayed by Judy Garland in Judgment at Nuremberg (1961), Brushfire (1962), The Man from the Diner's Club (1963), Pressure Point (1962), and Alvarez Kelly (1966).

Caine appeared in more than 750 live and filmed television programs, including the western series The Californians, Two Faces West, and The Travels of Jaimie McPheeters but is best remembered for his recurring role (37 episodes) as Major Wolfgang Hochstetter on the popular 1960s sitcom Hogan's Heroes (1965–1971).

From his early childhood in Tennessee, Caine had always been fascinated with the Appalachian five-string bluegrass banjo and began mastering it in the mid-1960s.