Miller was born in 1974 in the community of the Six Nations of the Grand River First Nation, Ontario, Canada. Miller became interested in music in his teens and by the late 1990s began touring with Buffy Sainte-Marie.
In 2002 Miller released his debut album Music is the Medicine on Winnipeg's Arbor Records. He received a 2003 Juno Award in the category Aboriginal Recording of the Year for "Lovesick Blues" from his album Music is the Medicine.
In 2006 Miller released his second album The Dirty Looks. Miller was honoured with a 2007 Canadian Aboriginal Music Award, in the category Best Rock Album, for his The Dirty Looks album. The album went on to win Miller a 2008 Juno in the category Aboriginal Recording of the Year.
He performed at the Closing Ceremonies of the Vancouver 2010 Winter Olympics with Eva Avila and Nikki Yanofsky.
In 2010 Miller released his third album Derek Miller with Double Trouble.
Miller has also appeared in supporting acting roles in film and television, including the films Moccasin Flats: Redemption, Fire Song and Point Traverse, and the television series Hard Rock Medical.
In 2015, he compiled an album titled "Rumble: A Tribute to Native Music Icons".