Stone was born in Houston, Texas to Gerald Whitney Stone, an economics professor, and Sheila Lois Belasco (who share the first names of the South Park character Kyle's parents). Stone's mother is Jewish and his father is of Irish descent; Stone "grew up agnostic" and considers himself "ethnically Jewish, but that's about all." He has a younger sister, Rachel. Stone was raised in the Denver, Colorado area, before moving to Littleton, Colorado. He attended Heritage High School in Littleton. He holds a degree in mathematics and film from the University of Colorado at Boulder, and was their first student to hold a double major in film and mathematics.
In 1992, Stone and Parker and Ben created Jesus vs. Frosty. It included four boys, two resembling Stan and Kyle, one called Kenny who looked like Cartman, and a fourth unnamed boy who looked like Kenny McCormick. Both Jesus and Cannibal! The Musical were made while they were students at the University of Colorado film school, studying under both Stan Brakhage and Jerry Aronson. After the duo releasedCannibal! The Musical, they were asked to make another animated short.They came down to two ideas: one a sequel to Jesus vs. Frosty, and one about a character that would later be recurring in South Park, Mr. Hankey. They chose to write about the four boys, and their decision ultimately opened the door for them to present a show (South Park) to Comedy Central. Stone and Parker produced 13 episodes for season 1. In 1997, they also released Orgazmo, a movie rated NC-17. In 1998, they starred in (but did not write or direct)BASEketball, another feature film, while being renewed for a second season of South Park. In 1999, Stone and Parker made South Park: Bigger, Longer & Uncut, which gave the series prominence. The film's music was nominated for an Academy Award, but lost. In 2001, the duo announced they would do 39 shorts between the lengths of 2 and 5 minutes. Although originally thought to be South Park-related, they decided they would do something different. The result was the shorts 'Princess'. The content was so extreme that it was cancelled after two shows aired. In 2001, they also created That's My Bush!, another television series. Despite great reviews, the show was cancelled after one season for its cost, reportedly $700,000 per episode.In 2004, they made a film titled Team America: World Police which many critics reviewed positively.In August 2007, South Park was renewed for three more seasons, 13, 14 and 15, each of them containing 14 episodes.
Stone is also a member of the band DVDA with Parker, for which he plays bass and drums. DVDA's songs have appeared in many of the duo's productions, including Orgazmo,BASEketball, South Park: Bigger, Longer & Uncut, and Team America: World Police.
Stone claimed to have been on acid with Trey Parker at the time of the 2000 Academy Awards, where they wore dresses popularized by Jennifer Lopez and Gwyneth Paltrow at previous awards shows.
On September 28, 2007, Parker and Stone acquired the US rights to the Canadian-made Kenny vs. Spenny, which premiered November 14, 2007 on Comedy Central with ten old and new episodes.
Stone and Parker collaborated with Avenue Q composer Robert Lopez on a musical about Mormons titled The Book of Mormon, which stars Andrew Rannells, Josh Gad, Nikki M. James and Rory O'Malley. It opened at the Eugene O'Neill Theatre on March 24, 2011, and is being produced by Scott Rudin and Anne Garefino. It is directed by Parker and Casey Nicholaw, and choreographed by Nicholaw.
In April 2010, Trey Parker and Matt Stone received a "warning" for allegedly representing the Prophet Muhammad in a bear costume: "We have to warn Matt and Trey [South Park creators] that what they are doing is stupid and they will probably wind up like Dutch director Theo van Gogh for airing this show." It was revealed in the next episode that the person in the bear costume was really Santa Claus and not the Prophet Muhammad; the "real" Muhammad was supposed to appear as well, but Comedy Central had him censored out against Stone and Parker's wishes.
Stone has one son. He identifies as an atheist.