Michael Andrew McKagan was born in Seattle, Washington, the youngest of eight children born to Elmer (Mac) and Alice (Marie) McKagan, a family with Irish1999 by Prince and Black Flag's Damaged. ancestors. They were a somewhat musical family with every member playing at least one instrument. It was his brother Bruce who taught him his first bass lines, though he developed his own skills playing along to

Although best known as a bass player, Duff also played drums in several bands, including, most notably, a stint with the legendary Seattle pop-punk band the Fastbacks, which he joined at the age of 16 in 1980. He also played drums in hardcore punk bands such as: The Fartz, Silly Killers (1982), and guitar in 10 Minute Warning (he was replaced by Daniel House of Skin Yard) He describes his home city as "a rowdy rock 'n' roll town with a hip underground." As well as drums and bass, McKagan also has the ability to play other musical instruments, he plays guitar and even played piano on the song Misery from the Loaded album Dark Days.

Answering an ad for a bass player in a local magazine, McKagan headed to California at age nineteen. In California he met guitar player Slash and drummer Steven Adler of the band Road Crew at L.A.'s legendary 24 hour deli and rock hangout Canter's. Duff expected some punk with a penchant for '70s rock, but found two long-haired guys instead.