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Michael Andrew McKagan grew up in Seattle's largely working-class University District, the youngest of eight children born to Marie and Elmer "Mac" McKagan. He has been called "Duff" since toddlerhood, to which he once referred as "an Irish thing". Following his parents' divorce, his mother supported the family by taking a job as a medical stenographer. He was taught how to play bass by his brother Bruce, further developing his skills by playing along with the albums 1999 by Prince and Damaged by Black Flag.

In April 1985, McKagan replaced bassist Ole Beich in Guns N' Roses, which was newly founded by singer Axl Rose and guitarist Izzy Stradlin of Hollywood Rose. McKagan's Road Crew bandmates Slash and Steven Adler joined the band two months later. After two days of rehearsal, the line-up played its debut gig at The Troubadour on June 6. In 1987, Guns N' Roses released its debut album, Appetite for Destruction, which to date has sold over 28 million copies worldwide, 18 million of which were in the United States, making it the best-selling debut album of all time in the U.S. The following year, the band released G N' R Lies, which sold over five million copies in the U.S. alone, despite containing only eight tracks, four of which were included on the previously released EP Live ?!*@ Like a Suicide.  In 1990, Steven Adler was fired from the band because of his heroin addiction; he was replaced by Matt Sorum of The Cult.  In May 1991, Guns N' Roses embarked on the two-and-a-half-year-long Use Your Illusion Tour. The following September, the band released the long-awaited albums Use Your Illusion I and Use Your Illusion II, which debuted at No. 2 and No. 1 respectively on the U.S. chart, a feat unachieved by any other group. In November 1991, Izzy Stradlin abruptly left the band; he was replaced by Gilby Clarke of Kill For Thrills. In 1993, the band released "The Spaghetti Incident?", a cover album of mostly punk songs, which proved less successful than its predecessors. McKagan took on lead vocals on four songs, including live favorite "Attitude", originally by the Misfits. That same year, McKagan released his debut solo album, Believe in Me, on which he sang lead vocals and played virtually every instrument.  In 1995, with Guns N' Roses largely inactive, McKagan formed the supergroup Neurotic Outsiders with Steve Jones of the Sex Pistols, John Taylor of Duran Duran, and his Guns N' Roses bandmate Matt Sorum. Originally a gathering of friends jamming together at the Viper Room in Hollywood, they released their self-titled album on Maverick Records in 1996. The band played a brief tour of Europe and North America, before disbanding in 1997. McKagan was the last member of the Appetite for Destruction lineup to leave Guns N' Roses, resigning as bassist in August 1997. McKagan had recently become a father and wrote about his decision to leave in his autobiography, stating "Guns had been paying rent on studios for three years now--from 1994 to 1997--and still did not have a single song. The whole operation was so erratic that it didn't seem to fit with my hopes for parenthood, for stability."
Duff McKagan