* Victor Mature as "The Narrator" (uncredited) and "Dimitrios Makropoulos"
* Peter Lorre as "Colonel Heller"
* Sydney Greenstreet as "Mr. Peters"
* Zachary Scott as "Mike Petrovic"
* Evelyn Keyes as "Helen"
* Richard Fraser as "The Man" (uncredited)
* George Zucco as "Dr. Panos"
* J. Edward Bromberg as "The Chief of Police"
* Geraldine Fitzgerald as "Mrs. Peters"
* Henry Daniell as "General Karras"
This film was a departure for director Jean Negulesco as it was the first film he directed after being an art director on several films.