One of his earliest appearances was on the radio show, The Jack Benny Program. During an episode which aired on April 9, 1950, Fontaine played a bum (named "John L. C. Silvoney") who asked Benny for a dime for a cup of coffee. The smallest coin Benny had to offer was a fifty-cent piece, so he gave it to him. The story Benny told about this event became a running gag during later shows. Fontaine's goofy laugh and other voice mannerisms made a hit with the audience, and Benny brought him back for several more radio shows between 1950 and 1952. He also later appeared in several of Benny's television shows.
On The Jackie Gleason Show, he played the character Crazy Guggenheim during Gleason's "Joe The Bartender" skits. His trademark was a bug-eyed grin and the same silly laugh he had done on Jack Benny's radio show. At the end of his Guggenheim sketch, he would usually sing a song, demonstrating a surprisingly good singing voice. In 1963, he released the album Songs I Sing on the Jackie Gleason Show, which collected some of these songs and reached number one on Billboard magazine's Top LP's chart in 1963.
Stan Freberg's voice characterization for Pete Puma in a 1952 cartoon was based on Fontaine's character voice. Fontaine received mention in satirist Tom Lehrer's 1965 song "National Brotherhood Week", from the album That Was the Year That Was. In the live show, Lehrer mentioned National Make-Fun-of-the-Handicapped Week, "Which Frank Fontaine and Jerry Lewis are in charge of, as you know." He also was the voice of Rocky the Rhino in Walt Disney's The Jungle Book until Disney cut the creature from the picture. He was also credited in Bobby Rydell and Chubby Checker's song "Jingle Bells Imitations", which was the flipside of their Jingle Bell Rock record.
Fontaine died of a heart attack on August 4, 1978 in Spokane, Washington. He had just completed a benefit show and accepted a check for $25,000, which he planned to donate for heart research, when he collapsed.
He was interred at Oak Grove Cemetery in Medford, Massachusetts, near to his last residence in Winchester, Massachusetts, a substantial house on Highland Avenue that is now the home of Winchester Community Music School.