First based in New York, then in Burbank, California, The Tonight Show became one of the best-loved programs in America. Even as Carson himself relied more and more on guest hosts during the 1980s, McMahon appeared nightly to perform his announcing duties and support the visiting hosts, who included Joan Rivers and Jay Leno.

Long before the final episode of The Tonight Show Starring Johnny Carson aired on May 22, 1992, McMahon made a name for himself in other areas first as a pitchman for products as diverse as Budweiser, Breck Shampoo, and Sara Lee Kitchens, and later as host of the long-running syndicated talent show Star Search, which debuted in 1983. McMahon also became well-known for his role as spokesman (along with longtime friend Dick Clark) for American Family Publishers (not to be confused with Publishers' Clearinghouse) and its sweepstakes.
McMahon has also pursued a career as an actor, with considerably less success. His interest was sparked by a brief stint as a replacement in the Broadway production of The Impossible Years in the mid-1960s. His feature films included The Incident (1967), Slaughter's Big Rip-Off (1973), Fun With Dick and Jane (1977), and Full Moon High (1981). More recently, McMahon appeared as himself in Love Affair (1994), starring Warren Beatty and Annette Bening, and earned a measure of praise for his supporting role on the short-lived 1997-1998 sitcom The Tom Show, starring Tom Arnold. In 1998, McMahon published a popular autobiography, For Laughing Out Loud: My Life and Good Times (he had previously published another memoir, Here's Ed, in 1976).

McMahon and his first wife, Alyce Ferrell, married while he was in college and had four children Claudia, Michael, Linda, and Jeffery before divorcing in 1976. With his second wife, Victoria Valentine, McMahon adopted a daughter, Katherine.
McMahon and Valentine divorced in 1989. He married Pamela Hurn in March 1992.
McMahon was extremely active in various charities. He made frequent appearances with Jerry Lewis on the Muscular Dystrophy Association annual telethon, served on the board of the Marine Corps Scholarship Fund, and also supported the United Negro College Fund.

McMahon died on June 23, 2009. He was suffering from bone cancer, among other illnesses, at the time. He was 86 years old.