Opatoshu played in a 1970 episode of Daniel Boone as "Tamenund", an aged Pequot Indian bent on revenge for his tribe's near-extinction.

On October 30, 1989, Opatashu guest-starred as the Tenctonese ex-slave Paul Revere in the episode "Night of the Screams", of the television series Alien Nation.

He also portrayed Herr Jacobi, one of the people who help Paul Newman and Julie Andrews escape from East Germany in Alfred Hitchcock's 1966 film Torn Curtain.

He played the Irgun leader (and Ari Ben Canaan's estranged uncle) in Otto Preminger's 1960 film Exodus.

In 1967, Opatoshu played Morris Kolowitz, the father of the main character David (Reni Santoni), in Carl Reiner's directorial debut Enter Laughing.

Opatoshu appeared on Broadway in Silk Stockings (1956), Once More, With Feeling (1958), The Wall (1960), Bravo Giovanni (1962), Lorenzo (1963), and Does a Tiger Wear a Necktie?

After serving with the Air Force in the South Pacific during World War II, Opatoshu returned to Manhattan and worked in radio, theater, television and films.