Bolton's hard rock band, Blackjack, once toured with heavy metal singer Ozzy Osbourne. He began recording as Michael Bolotin in 1975, after gaining his first major hit as a songwriter, co-writing "How Am I Supposed to Live Without You" for Laura Branigan, previously best-known for singing the disco-pop classic "Gloria".

Narrowly missing the Top 10 on the U.S. pop chart, Branigan took the song to number one on the Adult Contemporary chart for three weeks. The two sought to work with each other again, and their next of several associations was when Bolton co-wrote "I Found Someone" for Branigan in 1985. Her version was only a minor hit, but two years later, Cher resurrected the song, and with it her own singing career. Bolton co-wrote several other songs for both singers.

Bolton would achieve his greatest success in the late eighties and early nineties as a singer in the adult contemporary/easy listening genre. One of his first major hits was his 1987 interpretation of the Otis Redding classic, "(Sittin' On) the Dock of the Bay."

Always interested in soul and Motown classics, Bolton's success with that song encouraged him to tackle the standard "Georgia On My Mind," with which he had another hit. Most of Bolton's recordings are original material, however, he has also written songs for such artists as Barbra Streisand, Kenny Rogers, Kenny G, Peabo Bryson and Patti LaBelle.

Bolton's early songwriting collaborators included Doug James and Mark Mangold, and as his fame grew he began to cowrite with higher-profile writers such as BabyFace, Diane Warren, and Bob Dylan. As a singer, he has performed with Plácido Domingo, Luciano Pavarotti, José Carreras, Lucia Aliberti, Renée Fleming, Zucchero, Patti LaBelle, Céline Dion, Ray Charles, Percy Sledge, Wynonna Judd, and BB King.

Bolton's last charting single in the US was the 1997 hit "Go the Distance" (featured in the Walt Disney motion picture Hercules), which peaked at #24 on the U.S. pop chart.

In March 2007, Bolton toured South Africa for the first time. He was the headline act at Jacaranda 94.2 FM's two day concert.

Bolton recorded the song "New York, New York" (also on his Bolton Swings Sinatra album), for an album which was recorded in five days, Over the Rainbow. This was for an episode of the TV series, Challenge Anneka. The proceeds from the album went to children's hospices across the UK.

Bolton performed a duet entitled "Il Mio Amico" with the Italian singer Anna Tatangelo at the Sanremo Music Festival 2008. The song was originally sung by Tatangelo alone, but the duet version contained English lyrics as well. It is a song about the difficulties of being a homosexual in Italy, written by Tatangelo's partner, Gigi D'Alessio.