Two days after graduating from John R. Buchtel High School he took a bus to Hollywood in hopes of working for cousin Lester Cowan who had produced My Little Chickadee and several Marx Brothers films.

For the duration of his two-year hitch he ran movie projectors, wrote, produced and performed in soldier shows in Mississippi, attended courses at Fort McPherson, Georgia, and Washington and Lee University in Virginia (where he was classmates with future director Arthur Penn); Wayne also acted as booking agent of a hugely successful GI orchestra led by Ralph Cerasuolo, a sophisticated jazz violinist formerly known in New York City as "Leonardo of the Stork Club".

With half the cast as women in ill-fitting costumes and scraggly wigs, the show was to run for only three nights in Tauberbishofsheim, Germany[2] but its raucous, bawdy humor, robust singing, and dancing made it a roaring success that the Army recognized at once.

After raiding Stadttheater Heidelberg for colorful costumes, proper wigs, and scenery, the army sent the troupe on an extended eight-month tour throughout Germany,[4][5] Belgium, France, Italy, and Austria including stops at leading theatres in Berlin, Brussels, Paris,[6] Rome, and Vienna.

As an usher at Broadway's Alvin Theatre Wayne watched Ingrid Bergman star in Joan of Lorraine, and fetched tea for José Ferrer during the latter's celebrated run in Cyrano de Bergerac.

Following the Cyrano run Ferrer cast Wayne in his production of the Czech play The Insect Comedy whose performers included Ray Walston, Werner Klemperer, and Don Murray.

Fredd Wayne's big Broadway break came when he went to audition for Shakespeare's As You Like It starring Katharine Hepburn but was mistakenly pulled in to read for the Johnny Mercer – Bobby Dolan musical Texas, L’il Darlin’.

Critical success led to more Broadway credits such as Not For Children by Elmer Rice and following Ray Walston as Luther Billis opposite Mary Martin in the original London production of South Pacific.

Wayne's success in London – including a concurrent extended engagement at The Berkeley Cabaret – was followed by a role opposite Gene Kelly in MGM's Crest of the Wave, filmed in England and the Channel Islands.

It also led to American productions of South Pacific playing Billis opposite Gisele MacKenzie in Dallas, Vikki Carr in Kansas City, and Jane Powell in St. Paul, Minnesota.

He also made six guest appearances on Perry Mason, all shot in Hollywood, including the role of murder victim Jack Hardisty in the 1958 episode, "The Case of the Buried Clock".