Bolton began recording in 1975. This first album was self-titled using his original family name of Bolotin. Early in his musical career he focused on hard rock, with his band Blackjack once opening for heavy metal artist Ozzy Osbourne on tour. It was rumored that in 1983 Bolton auditioned for, but was denied, the lead vocalist position with Osbourne's former band, Black Sabbath. Bolton later stated this was untrue, saying "That rumor about me auditioning for Black Sabbath was only a rumor, I don’t know how on earth it started."
After anglicizing his family name to Bolton, he gained 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 pop hit "Gloria". Narrowly missing the Top 10 on the US pop chart, Branigan took the song to number one on the Adult Contemporary chart for three weeks in 1983. The two sought to work with each other again, and their next collaboration 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 achieved his greatest success in the late 1980s and early 1990s as a singer on the adult contemporary/easy listening charts. One of his first major hits was his 1987 interpretation of the Otis Redding classic "(Sittin' On) the Dock of the Bay". Redding's widow, Zelma Redding, said she was so moved by Bolton's performance "that it brought tears to my eyes. It reminded me so much of my husband that I know if he heard it, he would feel the same." 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. In 1991, Bolton released the album Time, Love & Tenderness which featured his Grammy Award-winning cover version of "When a Man Loves a Woman".
As a singer, he has performed with other artists such as: Lucia Aliberti, Patti LaBelle, José Carreras, Tony Cetinski, Ray Charles, Celine Dion, Plácido Domingo, Renée Fleming, Wynonna Judd, BB King, The Lonely Island, Luciano Pavarotti, Percy Sledge, and Zucchero. As a songwriter, he has written and collaborated on several songs for other artists as well.
Bolton's last Top 40 single in the US in his own right was the 1997 hit "Go the Distance" (featured in the Disney animated motion picture Hercules), which peaked at No. 1 on the US adult contemporary chart. He hired conductor Larry Baird (orchestral musical director/conductor/arranger for The Moody Blues, Three Dog Night, Al Jarreau, etc.) for his 2001 tour.
In 2006, Bolton and his then fiancee Nicollette Sheridan sang a duet, "The Second Time Around", for the album Bolton Swings Sinatra. 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.
For Over the Rainbow, an album which was recorded in five days, Bolton recorded the song "New York, New York", which was also on his Bolton Swings Sinatra album. 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.
Bolton's album Only a Woman Like You was released in 2001. The title song was co-written by Shania Twain. Bolton released his album One World One Love in the UK on September 21, 2009. The first single, "Just One Love", was released one week earlier.
In 2011, Bolton was featured as a guest vocalist in The Lonely Island's song "Jack Sparrow" on their Turtleneck & Chain album. His performance with the comedic hip-hop trio focused on his (intentionally) off-topic chorus and miscommunication with the group, and the video featured him dressed in costumes as Jack Sparrow from Pirates of the Caribbean, Forrest Gump, Erin Brockovich, and Tony Montana from Scarface.
As of February 2015, Bolton was working on the recording of a new studio album. He has collaborated with Indian musician A. R. Rahman for a song which was recorded in February 2011 for Gems – The Duets Collection.
In 2013 Bolton released the album Ain't No Mountain High Enough: A Tribute to Hitsville U.S.A., which featured duets with Kelly Rowland, Melanie Fiona and Orianthi.
In 2013 and 2014, Bolton appeared in Honda commercials in which he sings.
In 2015 Bolton sang on John Oliver's Last Week Tonight episode concerning the IRS.
In 2018, Bolton announced his intention to do a tour performance in Birmingham, England in November 2018, after two years since last time he visited the UK.
Bolton has made a number of cameo appearances in feature films and television, usually appearing as himself, such as in Meet Wally Sparks and The Nanny. Although he has been rumored to have appeared as an in Dune as a "spice-eyed" drummer, Bolton has stated in interviews that it is not him.
In August 2006, Bolton was one of Lucy Lawless's duet partners on the Fox network's program Celebrity Duets, which Simon Cowell's Syco Productions Company produced for the network.
Bolton was a contestant on the eleventh season of Dancing with the Stars. He and his dance partner Chelsie Hightower were the second couple to be eliminated, on September 28, 2010.
In 2015, Bolton starred in a Pizza Hut commercial as himself singing Jingle Bells while the family opens up their pizza order.
On May 10, 2018, it was announced that American Dream: Detroit (Exclusive), Michael Bolton film, would premiere on Tuesday, May 15, 2018 in Redford Theater. Despite Bolton being born in Connecticut, he fell in love with the city of Detroit and wanted to highlight its recent economic comeback. This documentary features interviews with several famous Detroit natives to include business moguls, singers and luminaries, including
Chris Ilitch, Jerry Bruckheimer, Francis Ford Coppola, Aretha Franklin, Smokey Robinson, and Alice Cooper. This "Love-Letter to Detroit" film is reported by the Crain's (a local business publication) in an article titled "Michael Bolton to appear at Redford Theatre for Detroit documentary premiere", written by Annalise Frank.