Saget was born in Philadelphia, Pennsylvania and then moved to Munster, Indiana when he was two. He attended Abington Senior High School, and he has since been enshrined in its Hall of Fame. He later enrolled at Temple University, where he made a student film, "Through Adam's Eyes", which was honored with an award of merit in the Student Academy Awards in 1977.

After college, Saget nourished his career with relatively small-scale gigs before achieving national fame with his role on Full House as the widower father of a large brood including, among other children, the Olsen twins. In 1989, he won what was to be another long-running gig as host of America's Funniest Home Videos.

In contrast to his mild, family-friendly manner on those well-known television programs, Saget is also known for raunchy, unabashedly vulgar stand-up comedy routines. His performance of the traditional joke "The Aristocrats" (in the 2005 movie of the same name) is reputed to be one of the foulest (and funniest) retellings ever attempted; in any case it is one of the film's lengthiest, filthiest and most imaginative renditions of the joke. Saget has been alternatively lauded as one of the "The Greatest Comedians of All Time" as well as "The Worst Comedians of All Time" due to his vulgar comedic nature, which either attracts fans or repulses them. His routines typically have Saget making fun of how geeky and dorky Danny Tanner was, and how cheesy and corny Full House was. Regardless, like others on the show, he remains close to his cast mates, and even at times tours on the stand-up circut with Dave Coulier.

After a failed attempt at another sitcom, Raising Dad, in 2001, Saget has turned to directing. He is currently acting on stage in New York and serves as the narrator of the CBS sitcom How I Met Your Mother, which debuted September 19, 2005.

Saget's sister died of scleroderma. Her life story was the inspiration for Saget's semi-autobiographical ABC television movie, For Hope, which he directed. Saget is currently a board member of the Scleroderma Research Foundation, the only organization in the United States dedicated solely to finding a cure for the disease.