Most was born to a Jewish family in Brooklyn, New York. He lived in Flatbush, Brooklyn, New York, and graduated from Erasmus Hall High School in 1970. He attended Lehigh University for three years from 1970 to 1973, but did not graduate. Originally intending to study engineering, he changed his major to Business after his first semester. He made plans during his junior year to spend the summer of 1973 in search of acting jobs in Hollywood before completing his studies at Lehigh. Instead, he landed the Ralph Malph role on his third audition and moved to California to pursue acting full-time. Interestingly, Most appeared on the 15th and final episode of Room 222, entitled "Jason and Big Mo", in the role of Louie, the red-headed class wisecracker. David Jolliffe had handled the role of Bernie, the red-headed class wisecracker, for all prior appearances. Room 222 aired for the last time in January 1974, just as Happy Days began, and on the same network, ABC.
Most performed as a voice actor on several Saturday morning cartoon series. Among these roles were: Ralph Malph on The Fonz and the Happy Days Gang (1980); Eric the Cavalier in Dungeons & Dragons (1983); and Stiles on Teen Wolf (1986–1989). Most had a cameo as himself in the fifth season Family Guy episode "It Takes a Village Idiot, and I Married One" in 2007.
Most married Actress Morgan Hart in 1982. They have two daughters and live near Los Angeles, California. Morgan's mother was Margaret Hart Ferraro.
Most had a role as a regular cast member on Happy Days, appearing through to the final (11th) season. Most has appeared in other film and television work. Film credits include EDtv (1999), Planting Melvin (2005) and The Great Buck Howard (2008). He also made the regular round of guest appearances on TV shows like Emergency!, CHiPs, Baywatch, The Love Boat, Sliders, Star Trek: Voyager, Diagnosis: Murder and Glee. He also made an appearance on Charles in Charge, alongside his former Happy Days co-star, Scott Baio. He plays a man who has just won the lottery and, as part of the cameo joke, he runs up to Scott Baio and waving the winning ticket shouts, "It looks like Happy Days are here again!" He also receives several looks from Scott Baio that suggests familiarity throughout the episode. He is sometimes credited as "Donny Most."
On April 19, 2011, Most and four of his Happy Days co-stars, Erin Moran, Marion Ross, Anson Williams and the estate of Tom Bosley, who died in 2010, filed a $10 million breach-of-contract lawsuit against CBS, which owns the show, claiming they had not been paid for merchandising revenues owed under their contracts. The cast members claimed they had not received revenues from show-related items, including comic books, T-shirts, scrapbooks, trading cards, games, lunch boxes, dolls, toy cars, magnets, greeting cards and DVDs where their images appear on the box covers. Under their contracts, they were supposed to be paid five percent from the net proceeds of merchandising if their sole image were used, and half that amount if they were in a group. CBS said it owed the actors $8,500 and $9,000 each, most of it from slot machine revenues, but the group said they were owed millions. The lawsuit was initiated after Ross was informed by a friend playing slots at a casino of a "Happy Days" machine on which players win the jackpot when five Marion Rosses are rolled.
In October 2011, a judge rejected the group's fraud claim, which meant they could not receive millions of dollars in potential damages. On June 5, 2012, a judge denied a motion filed by CBS to have the case thrown out, which meant it would go to trial on July 17 if the matter was not settled by then. In July 2012, the actors settled their lawsuit with CBS. Each received a payment of $65,000 and a promise by CBS to continue honoring the terms of their contracts.
As of 2017, Most is performing in a U.S. tour, "Donny Most Sings and Swings," performing a set of 1950s swing music with a 7-piece backing band.
