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Mulrooney was born and raised in Brooklyn, New York. He began his career on the Comedy Tonight variety show in the 1970s. He wrote comedy for The Tonight Show, and also performed stand up for The Tonight Show studio audience warm-up for over 165 episodes.
Mulrooney competed on Star Search and lost, but it helped his early career, since he was hired to work for the program, writing comedy and doing audience warm up.
After relocating to Los Angeles, California, Mulrooney auditioned at the world famous Improv Comedy Club in Los Angeles, where he met and befriended Budd Friedman. Friedman hired him on the spot to perform at all of his clubs.
After Joan Rivers left as host of The Late Show on the Fox network in 1987, Mulrooney was asked to replace her. After a few months, The Late Show was cancelled due to low ratings and competition with The Tonight Show's Johnny Carson and Nightline's Ted Koppel.
Mulrooney appeared on Comedy Tonight in its syndicated format in the 1980s. He hosted Comic Strip: Live, first for a year as a local show on KTTV in Los Angeles in 1988, continuing when Fox TV programming executives expanded the show to Fox-owned stations, then network-wide on Saturday nights, for an additional year.
He appeared on other TV shows such as An Evening at the Improv, Hollywood Squares, and others, as well as appearances on Showtime, HBO and Comedy Central and filling in as guest host for Pat Sajak on The Pat Sajak Show.
Mulrooney wrote and starred for two seasons in a sitcom called Midtown North which aired on Comedy Central.
Mulrooney developed alcohol dependency and sought rehabilitation, as he has admitted. After recovery, he changed his routines to include spirituality mixed with humor. Appearances include wisdom from his experiences in life.
In 2010, Mulrooney travelled to the Middle East to entertain troops as part of the Locked, Loaded and Laughing Out Loud - Incoming Comedy tour.Locked, Loaded and Laughing Out Loud Armed Forces Entertainment</ref>
- "Comic Strip Live" (1989) TV Series .... Host (1989–1990)
- Great Balls of Fire! (1989) .... Talk Show Host
- Ryder P.I. (1986) .... Gang Leader
Television appearances include
- Penthouse Vegas Fox
- Tough Crowd with Colin Quinn Comedy Central
- Hollywood Squares Syndicated
- Comedy Tonight Syndicated
- Star Search Syndicated
- Candid Camera Co-host CBS
- The Late Show Host Fox
- King of the Mountain Host Fox
- Comic Strip Live Host Fox
- The Pat Sajak Show Guest Host CBS
- An Evening at the Improv A&E
- Caroline’s Comedy Hour A&E
- Comedy Album Host A&E
- Comedy on the Road A&E
- A Pair of Jokers A&E
- A Different Point of View Host A&E
- Playboy Channel Comedy Hour
- Anything for Love Host Syndicated
- The Good Life Series Regular NBC
- Midtown North Series Regular Comedy Central
- 105.1 FM "MIX 105" New York, N.Y. Morning show host
- 105.1 FM "THE BUZZ" New York, N.Y. The John and Abbey show
- 106.5 FM "PYX 106" Albany, N.Y. Wakin' up with the Wolf and Mulrooney
- 100.7 FM WMMS "THE BUZZARD" Cleveland, Ohio Wakin' up with the Wolf and Mulrooney
- 93.7 FM "HOT TALK RADIO" Albany, N.Y. Mulrooney in the Morning
- 2009 104.9 FM WZMR "THE EDGE" Albany, N.Y. Mulrooney in the Morning with Mike the Enforcer
- 2010 101.5 FM WPDH Poughkeepsie, N.Y. Wakin' Up with Coop and Mulrooney
- 2010 Howard 101 Sirius Satellite Radio New York, NY
- Present 102.5 FM "Funny" Kansas City, Mo 24/7 Comedy
- Brooks, Tim; Marsh, Earle (2007). The Complete Directory to Prime Time Network and Cable TV Shows, 1946-Present. Random House Publishing Group, p. 277. ISBN 978-0-345-49773-4.
- Staff (December 21, 2007). American Comics Hold Benefit Tour in Israel IsraelNN.com; Arutz Sheva (Israel).
- Locked, Loaded and Laughing Out Loud Incoming Comedy Tour - Governor's Comedy Club May 1, 2010.
- Moving And Shaking At Albany's Edge allaccess.net; WZMR. Press release. January 6, 2009.
- WPDH Brings Aboard John Mulrooney To Co-Host Wakeups allaccess.net; WPDH. Press release. June 10, 2010.