Duff was born as Michael McKagan on February 5, 1964, in Seattle, Washington. He was the youngest of 8 children in a Catholic family.
The music took overhand during his school years. He has said that he played in approximately 31 bands, including Ten Minute Warning (drummer/guitarist) that released an album in 1998, the Living (drummer), Silly Killers (drummer), the Fastbacks (drummer) and Hobo Skank (drummer). He played drums and guitar. Duff had even been asked to join an English band called Angelic Upstarts. But by joining them he'd have to move to England, so Duff declined the offer.
In the year of 1983 Duff and his friend Greg Gillmore decided to move to LA. Duff had heard that LA was full of talented guitarists, so he switched to bass guitar.
In 1985 he answered an ad for a bass player in Recycler. The man behind the ad was Slash. Duff, Slash and Slash's buddy Steven Adler formed the band Road Crew which split up and became Hollywood Rose which also split up and fused with the singer Axl Rose, and the rhythm guitarist, Izzy Stradlin on June 6 1985.
Duff was known to have serious problems with alcohol and drugs during the years in Guns N' Roses. He remembers his first encounter with alcohol quite clearly: "My old man gave me some whiskey when I was real little. It was Hawaiian whiskey, and it had this real long Hawaiian name. He said, 'Take a swig and pronounce the name.' After about four swigs I couldn't pronounce the name because I was already too drunk."
He got married to his girlfriend Mandy Brixx when Guns toured with Iron Maiden in 1988. They divorced on April 1, 1990.
He made his debut as a lead vocalist in Guns on the song "So Fine", found on Use Your Illusion II.
In 1993 he married to Linda Johnson. That marriage lasted until 1996.
Duff released a solo album in 1993 called "Believe In Me". He made a tour with a band called DUFF (which included GN’R tour keyboardist Teddy Andreadis). On May 10, 1994 Duff was close to death. As a result of his long-time alcohol and drug abuse, his pancreas had exploded. After this Duff was ordered not to ever take a drink again by his doctor. So he shaped up and started training martial arts and living a healthy life in general.
On March 10, 1995, opened the Hard Rock Hotel in Las Vegas, Nevada. A lot of artists performed and Duff was part of the houseband called Wayne Neutron. The other members were Matt and Steve Jones (ex-Sex Pistols. They played with artists such as Billy Idol, Iggy Pop, Bo Diddley, Izzy Stradlin and Seal. The idea of Neurotic Outsiders was born.
It took until August the next year till their self-titled album was released on Maverick Records. The members were Duff, Matt Sorum, John Taylor (ex-Duran Duran)and Steve Jones. They toured in North America and Europe in the fall. In the summer of 1997 was Duff's daughter Grace born.
On May 5, 1998 was Ten Minute Warning’s selftitled debut album released.
Duff played on Izzy Stradlin's second solo album, "117 degrees" that was released this year
Throughout 1998 Duff worked on his second soloalbum, "Beatiful Disease." But unfortunately the album was never released due to the record company merger
between A&M, Geffen and Interscope. But Duff and his new band, LOADED started a mini-tour anyway in March 1999. On two of the dates they recorded a live album that was released through Duff's official site on May 27. At that time they were out on their second mini-tour, including 14 dates over the US.
After that it was quite silent about Duff for a while. He married his girlfriend Susan Holmes in August of 1999.
In the end of the year Duff once again appeared on an Izzy Stradlin album. This was called "Ride On", and was only released in Japan since Izzy had been dropped from Geffen along with Duff in 1999. To promote the album they went on a four-date tour in the middle of April of 2000.