Distefano, who is of mostly German descent[2] (and also has some Italian and Irish ancestry),[3][4] grew up in the Ridgewood neighborhood of Queens and attended Archbishop Molloy High School.

Distefano was recruited to play for St. Joseph's College Brooklyn's D-III basketball team in 2002.

[4] Following an appearance on Late Night with Seth Meyers,[13] Distefano began his first national U.S. tour in September 2015 with Monster Energy Outbreak Presents.

[14] He was one of two American announcers on Season 2 of Netflix's Ultimate Beastmaster, which was released on the streaming service on December 15, 2017.

In January 2019, his first hour standup special Chris Distefano: Size 38 Waist premiered on Comedy Central, which included a personal welcome on stage by Chazz Palminteri.

[17] He would later go on to sell out his first two shows at the Gramercy Theatre that March, during which he recorded his second special, Speshy Weshy.

[18] Distefano, an avid sports fan, has hosted episodes of shows including MLB's Off The Bat and MSG's The Brackets.

He was invited by the New York Mets to throw the first game pitch in 2021,[19] and set off the Vegas Golden Knights' pre-game siren alongside friend and fellow comedian Andrew Santino in March 2022.