Pirner was born in Minneapolis,Minnesota. He taught himself how to play the drums. By age 20, Pirner started his career drumming with a punk band called Loud Fast Rules as part of the Minneapolis scene, together with Karl Mueller (bass) and Dan Murphy (guitar). When Pirner switched to singing and playing rhythm guitar, Pat Morley joined on drums. Morley was later replaced by Grant Young, and the band changed their name to Soul Asylum. After touring the United States for a number of years they gathered a cult following of fans, but did not quite reach commercial visibility. Pirner at the time was the band's songwriter and he produced the album, Coup De Grace, by the Minneapolis metal band the Coup de Grace in 1990.
The band achieved commercial success and visibility on MTV and VH1 with the 1992 single "Runaway Train", followed by another hit song, "Black Gold"; both from their album Grave Dancers Union. As Soul Asylum grew in popularity, Pirner was seen guesting on albums of differing genres, including artists like Paul Westerberg, Jason Karaban, Mike Watt, The Autumn Defense and Victoria Williams. His disheveled appearance and blonde matted dreadlocks made an unmistakable impression on fans and critics alike, making Pirner easily recognized and associating the band with the grunge scene.
By 1999, Soul Asylum went into hiatus after making 1998's Candy from a Stranger, which sold the fewest number of copies of the three albums released at that point (after Grave Dancers Union and Let Your Dim Light Shine (1995), which yielded the big hits "Misery" and "Just Like Anyone"). After four years, Soul Asylum reunited and started writing songs in the studio. Bassist Karl Mueller died on June 17, 2005, at the age of 42 from esophageal cancer. About a year after his death, Soul Asylum released The Silver Lining on Legacy Recordings, which was dedicated to Mueller. About half the songs on the album were recorded with the late bassist, such as "Lately", "Slowly Rising" and "Standing Water". The first hit from this album was "Stand Up And Be Strong". Soul Asylum toured with their new line-up, which consisted of Pirner on guitar and vocals, Dan Murphy on lead guitar, Michael Bland on drums and Tommy Stinson on bass (as well as John Fields standing in on bass and piano for Mueller). Soul Asylum's latest effort was released on July 17, 2012, titled Delayed Reaction.
Jared Gertzen also quotes Pirner as "One of the best Singer/Songwriters to come out of Minnesota since Prince".
Pirner had a small role in the film Reality Bites in 1994. He was also part of the all-star band assembled for the soundtrack of the 1994 film Backbeat. Pirner also contributed to the soundtrack of Kevin Smith's 1997 film Chasing Amy with an instrumental song called "Tube Of Wonderful". The song "Can't Even Tell" is featured in Smith's Clerks, and Smith used "Misery" in the sequel, Clerks II.
In 2002 Pirner released his first solo album entitled Faces & Names on Ultimatum Music. He also contributed guest vocals on the song "Chillout Tent" in The Hold Steady's 2006 release, Boys and Girls in America.
Pirner lived in Bywater, New Orleans, Louisiana for a time and still maintains a residence and recording studio in New Orleans.
Faces & Names, (2002), (Ultimatum Music)
Dave Pirner appears on the track Whole World Is Watching by Within Temptation on their 2014 release, Hydra.