- Wrote the Stefon sketches on Weekend Update with Saturday Night Live (1975) cast member Bill Hader. Bill Hader and John Mulaney got the idea of Stefon from a shy café worker and a friend who opened many clubs that 'had everything'.
- Attended Georgetown University with comedian Nick Kroll.
- Grew up in Chicago.
- Won the 2018 Emmy Award in the Outstanding Writing for a Variety Series category for John Mulaney: Kid Gorgeous at Radio City (2018).
- Owned a French Bulldog named Petunia.
- Parents are Ellen, a law professor, and Charles (Chip) W. Mulaney, Jr., an attorney.
- On July 5, 2014, Mulaney married make-up artist Annamarie Tendler.
- Studied English Literature at Georgetown University.
- Had two sisters and two brothers, the younger of which is deceased.
- Maternal great-grandfather was George J. Bates, a mayor of Salem, Massachusetts, from 1924 to 1937, who also served as a congressman (R) from that state, from 1937 to 1949. His great-uncle, William H. Bates, was also a congressman (R) from Massachusetts, from 1950 to 1969.
- Is a fan of the television show Law & Order: Special Victims Unit (1999).
- Has a son, with Olivia Munn, named Malcolm Mulaney, born on November 24, 2021.
- Mulaney attended St. Clement School and then St. Ignatius College Prep.
- Expecting child with actress/model Olivia Munn [September 2021].
- He is of Irish, and one eighth German, descent.
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