His father sang harmonies in a barber shop quartet and most of his seven brothers and sisters could play at least one instrument. It was his brother Bruce who taught him his first chords on the bass guitar. Between the ages of 15 and 19 Duff estimates that he played in over 30 bands in Seattle alone. He played not only bass, but drums and guitar as well and at one stage was close to becoming drummer for the English punk band the Angelic Upstarts. However, the thought of moving to England to live was too much for the young Duff and he decided to remain in Seattle with his old band. The Seattle music scene was at the time quite limited though and so, just 20 years old, Duff decided to head for LA. It was this move that prompted a return to the bass because as he would recall "...I had heard all these stories about LA, you know, that there were millions of great guitar players there already. And I really didn't think that I was good enough to be one of the top guys."

Guns N' Roses was not the first band that Duff met up with after arriving in LA though. He had been given the phone number of a guy named Slash, who Duff assumed to be "...some old punk guy with a name like that." Slash and his friend Steven Adler were in a "band" called Road Crew who were permanently looking for musicians. Duff and the two members of Road Crew met at a Jewish delicatessen called Cantners. At this time Duff's appearance was still very much faithful to his punk roots, including the almost obligatory dyed hair, which in Duff's case was various shades of red, black and blond. So Duff visited Cantners "...still expecting to find some old punk rock guy. Slash and Steven were there with their girlfriends and they were all completely wasted. And their girlfriends immediately thought I was a homo because of my hair..."

Nevertheless, Duff joined Road Crew in the spring of 1985. Road Crew's lack of organisation, lack of gigs and lack of rehearsals would soon take it's toll however and Duff began scouting the Musicians Wanted sections of the local papers again. What he found was Axl's number. Duff realised that the Guns N' Roses lineup as it was far from perfect. He worked hard to arrange some gig dates and when Rob Gardener and Tracii Guns pulled out of a series of West Coast dates Duff invited the two-man Road Crew team to join them. Slash and Steven jumped at the chance, with the initial intention of stealing Axl away for their own band.

Duff proved to be the vital link between Road Crew and Guns N' Roses. Although the "Hell Tour" was, by all accounts, a failure on the musical front it brought the two bands together and offered the chance for friendships to blossom. Guns N' Roses now had a sense of purpose and set about getting serious.