Born Eugene Klass to a Jewish family in New York City, New York, he exhibited early skills with his singing and violin playing. He adopted his professional name in honor of John Barrymore.

He appeared on Broadway in Catherine was Great in 1944, and, many years later, he starred in the musical La Cage aux Folles (based on the French film of the same name about a gay couple with a straight son) with George Hearn as his life partner/spouse. For his contribution to live theater, Gene Barry has a star on the Hollywood Walk of Fame at 6555 Hollywood Blvd.

An early film role was in the 1953 production of The War of the Worlds. He makes a cameo appearance in Steven Spielberg's 2005 War of the Worlds, along with his 1953 co-star Ann Robinson.

Known for his suave manner, Barry starred on television in Our Miss Brooks, Bat Masterson, The Name of the Game, and Burke's Law. He won the 1965 Golden Globe for Burke's Law. Barry played the lead in the most famous episode of The Name of the Game, a science fiction story directed by Steven Spielberg and written by Philip Wylie called "L.A. 2017."

Barry has appeared in a number of films, television programs, and stage shows. His wife of 60 years, Betty Clair Kalb, died in 2003. He has two sons, Michael and Frederick, and a daughter, Elizabeth.

Mr. Barry was Cub Scout Master of Pack 100 in Beverly Hills, California in the mid 1950s.