As a handsome, debonair leading man in 40 films over the next 14 years, he starred in comedies, dramas, and musicals. In the 1950s he worked on Broadway and in television, and was the host of NBC's International Showtime from 1961 to 1965. Returning to film work in his later years, Ameche enjoyed a fruitful revival of his career beginning with his role as a villain in Trading Places (1983) and won the Academy Award for Best Supporting Actor for his performance in Cocoon (1985).
Don Ameche was born as Dominic Felix Amici on May 31, 1908, in Kenosha, Wisconsin. His father, Felice Amici, was a bartender from Montemonaco, Ascoli Piceno, Marche, Italy. His mother, Barbara Etta Hertel, was of Scottish, Irish, and German ancestry. Ameche was the second-oldest of eight children; he had three brothers, Umberto (Bert), James (Jim Ameche), and Louis, and four sisters, Elizabeth, Catherine, Mary and Anna. Ameche attended Marquette University, Loras College, and the University of Wisconsin–Madison, where his cousin Alan Ameche played football and won the Heisman Trophy in 1954.
Ameche had done well in college dramatics at the University of Wisconsin, and when a lead actor for a stock company production of Excess Baggage did not turn up, a friend persuaded him to stand in for the missing actor. He enjoyed the experience and got a juvenile lead in Jerry For Short in New York, followed by a tour in vaudeville with Texas Guinan until she dropped him from the act, dismissing him as "too stiff".

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