Kayne studied musical theater in college before moving into comedy and writing.[6] He became a performer at the Upright Citizens Brigade Theatre in New York City.[7] He co-created the web series Terrible Babysitters with D'Arcy Carden, which screened at SXSW, and co-wrote and starred in the pilot Good Dads, which was presented at the New York Television Festival.[7] He served as a creative consultant for Billy on the Street and wrote for the pilot presentation of @midnight.[8]
Kayne joined the writing staff of The Late Show with Stephen Colbert on CBS.[3] His work on the show has earned him a Peabody Award and a Writers Guild of America Award.[8] He has received multiple Primetime Emmy Award nominations as a writer on The Late Show and on Stephen Colbert's Election Night 2020: Democracy's Last Stand: Building Back America Great Again Better 2020 on Showtime.[3][9]
As an actor, Kayne has appeared in television series including Severance on Apple TV+; High Maintenance and White House Plumbers on HBO; and Late Night with Seth Meyers as a stand-up performer.[7] He has also appeared on The Chris Gethard Show.[7]
In November 2019, on the tenth anniversary of his son Fisher's death, Kayne wrote a thread on Twitter about grief and loss that received more than 140,000 responses.[4][5] The thread, and the public response to it, became the basis for his solo show Sorry for Your Loss.[10]
The show premiered in 2023 at the Minetta Lane Theatre in New York City, produced by Audible Theater and directed by Josh Sharp.[1] The Off-Broadway run was extended ahead of its May 8 opening night.[10] An audio recording was released on Audible and was named a Best of Audible selection in 2023.[11]
Sorry for Your Loss received nominations for the 2024 Lucille Lortel Award for Outstanding Solo Show and the 2024 Drama Desk Award for Outstanding Solo Performance.[2] A filmed version of the special was released on Dropout on the 27th of March 2026 as part of the second season of the platforms stand-up comedy series "Dropout Presents."[12]