Musto was born in Brooklyn, New York. He wrote movie reviews as a child, and acted in plays as a way to overcome his shyness. He graduated from New Utrecht High School in Brooklyn (the very same high school visible from the subway shown in the opening credits of the television show "Welcome Back, Kotter") in 1972 and from Columbia College of Columbia University in 1976, where he performed with the Barnard Gilbert and Sullivan Society.

Musto began his Village Voice column in 1984, after having already written some feature stories for the publication. He is a recurring guest on several TV shows including Countdown with Keith Olbermann and others on the E! channel. He is openly gay and is published regularly in several gay publications, including Out Magazine and ShowPeople. He appeared in drag in a blue dress in the all drag queen music video for Cyndi Lauper's single "Hey Now ", and as a reporter in the film Garbo Talks.

Musto was named Best Gossip Columnist in a poll conducted by nycsidewalk.com, and in 2002, a UPI profile of Musto called him "one of the wittiest stylists in the English language". Musto is also known as the author of articles in the Village Voice that cited rumours about the murder of Angel Melendez. The result of this and subsequent publications by Musto regarding the murder brought to attention a case in which police were otherwise uninterested and resulted in the trial and conviction of Michael Alig and Robert "Freez" Riggs.

On the June 14, 2007 edition of Countdown with Keith Olbermann, Musto coined the word 'celebutard' (combination of the words 'celebrity', 'debutante', and 'retard') to describe celebutantes Paris Hilton and Lindsay Lohan.

Mike was also part of the "Club Kid" scene in New York during the late 80's early 90's. You can see him in the youtube video, Michael Alig Outlaw party at Mc Donalds

Musto has authored three books:

• Musto, Michael. (June 12, 1986) Downtown-V285 Publisher: Vintage. ISBN 0-39474-285-0
• Musto, Michael. (September 1989) Manhattan on the Rocks. Publisher: Henry Holt & Co ISBN 0-80501-032-7
• Musto, Michael. (January 1, 2007) La Dolce Musto: Writings by the World's Most Outrageous Columnist Publisher: Carroll & Graf ISBN 0-78671-879-X

Musto has provided requested contributions to four published works:

• Contributed foreword to Boas, Gary Lee. (January 2000) Starstruck: Photographs from a Fan Publisher: Dilettante Press ISBN 0-96642-725-4
• Contributed as an author to McMullan, Patrick. (November 2003) so8os: A Photographic Diary of a Decade Publisher: powerHouse Books. ISBN 1-57687-187-8
• Contributed as an author to Hastreiter, Kim. (September 14, 2004) 20 Years of Style: The World According to Paper Publisher: Amazon Remainders Account. ISBN 0-060-72302-5
• Provided afterword in Haden-Guest, Anthony (October 2, 2006) Disco Years Publisher: powerHouse Books ISBN 1-57687-325-0