Raised in an Italian-American family in Bensonhurst, Brooklyn, New York, he graduated with honors from Hunter College, earning a bachelor's degree in Comparative Politics.
Jeni first received recognition through a series of Showtime stand-up specials and frequent appearances on The Tonight Show. Top executives at HBO noticed Jeni's talent, and he was soon picked up for his first appearance on The HBO Comedy Hour in 1992, titled "Richard Jeni: Platypus Man."
The show was well-received and Jeni would return for two more shows, going on to receive a CableACE Award for one of his HBO specials. Jeni would also star on the short-lived UPN sitcom Platypus Man and appear in the Jim Carrey film The Mask. And also appeared in The Aristocrats, National Lampoon's Dad's Week Off, and Burn, Hollywood, Burn. He also starred in commercial campaigns for Certs and Arby's, and won a Clio Award for his work as a writer/performer in an advertising campaign for the American Dairy Association.
Jeni appeared on The Tonight Show more than any other stand-up comedian, dating back to when the program was hosted by Johnny Carson. Jeni's death was referenced on the show by Jay Leno on March 12, 2007, with accompanying footage of Jeni's last appearance on The Tonight Show.
In 2004, Jeni was ranked #57 on Comedy Central's list of the 100 greatest standups of all time; he served on the panel responsible for this ranking.