Born in Malone, New York, Mould lived in several places, including the Minneapolis-St. Paul area where he then attended Macalester College. There, he formed Hüsker Dü in the late 1970s, with drummer/singer Grant Hart and bass guitarist Greg Norton. Hüsker Dü first gained notice as a punk rock group with a series of recordings on the independent label SST Records. One of the first 1980s underground bands to sign a contract with a major record label (Warner Bros. Records), Hüsker Dü found only moderate commercial success, but were later often cited as one of the key influences on 1990s alternative rock.

In the late 1980s, Hüsker Dü broke up acrimoniously amid members' drug abuse and personal problems. Mould and Grant Hart, the band's other songwriter and vocalist, still take occasional jabs at each other in the press, though the two revisited their Hüsker Dü back catalog together at a 2004 benefit concert for an ailing friend, the late Karl Mueller of Soul Asylum.

After Hüsker Dü broke up in 1988, Mould sequestered himself in a remote farmhouse in Pine City, Minnesota, quit drinking and drugs, and wrote the songs that would make up his first solo album. Signing to the newly-formed Virgin Records America label, 1989's Workbook eschewed Mould's trademark wall-of-noise guitar for a stripped-down, atmospheric sound featuring acoustic guitars and cellos. 1990's jagged Black Sheets of Rain put Mould in more familiar territory, recalling Hüsker Dü's loudest, angriest moments.

Mould then formed the group Sugar, a college/alternative radio favorite in the mid-1990s. Along with extensive touring, Sugar released two albums, an EP and a B-sides collection before breaking up.

Mould returned to solo recording, releasing a self-titled album in 1996 (which is often referred to as Hubcap because of the cover photo) and 1998's The Last Dog and Pony Show.

During a stint living in New York City in the late-1990s, Mould's tastes took a detour into dance music and electronica. Those influences were clear on his 2002 release Modulate, which featured a strong electronica influence to mixed critical reviews. To pursue this sound, Mould also began recording under the pseudonym LoudBomb (an anagram of his name). He has released one CD so far under this name.