Born in New York City to a Jewish family, Chwatt received the nickname as a young man, when he worked as a waiter in Dinty Moore's Tavern in The Bronx — his uniform's shiny buttons and his bright red hair caused patrons to give him the name he would later perform under.

From 1947 to 1951, he was married to actress Roxanne Arlen, who would have been only 16 if her Wikipedia year of birth (1931) is accurate. His next marriage was to Helayne McNorton, from December 8, 1949 until 1963, when they divorced. His last marriage was to Alicia Pratt, from January 27, 1964, until her death in March 2001. Pratt conducted a long-term lesbian affair during their marriage.

After years performing burlesque and doing comedy routines in the Borscht Belt, Buttons received his own variety series on television in 1952 — The Red Buttons Show ran for three years and achieved high levels of success. His catchphrase from the show, "strange things are happening", entered the national vocabulary briefly in the mid-1950s.

After his Oscar-winning role in Sayonara, Buttons performed in numerous feature films, including Hatari!, The Longest Day, Harlow, The Poseidon Adventure, They Shoot Horses, Don't They?, and Pete's Dragon. He also made memorable TV appearances, including It's Garry Shandling's Show.

He became a nationally recognizable comedian, and his "Never Got A Dinner" sketch was a standard at the Dean Martin roasts for many years.