Ikue Mori was born and raised in Japan. She says she had little interest in music before hearing punk rock. In 1977, she went to New York City, initially for a visit, but she fell into the music scene, and has remained in New York since.

Her first musical experience was as the drummer for seminal no wave band DNA, which also featured East Village hero, Arto Lindsay. Though she had little prior musical experience (and had never played drums), Mori quickly developed a distinctive style: One critic describes her as "a tight, tireless master of shifting asymmetrical rhythm", while Lester Bangs wrote that she "cuts Sunny Murray in my book." His comment is no small praise, as Murray is widely considered a major free jazz drummer.

After DNA disbanded, Mori became active in the New York experimental music scene. She abandoned her drum set, and began playing drum machines, which she sometimes modified to play various samples. According to Mori, she was trying to make the drum machines "sound broken." Critic Adam Strohm writes that she "founded a new world for the instrument, taking it far beyond backing rhythms and robotic fills." In recent years she has used a laptop as her primary instrument, but is still sometimes credited with "electronic percussion".

In 1995, she began collaborating with Japanese bass guitarist Kato Hideki (from Ground Zero), and together with experimental guitarist Fred Frith (from Henry Cow), they formed Death Ambient. The trio released three albums, Death Ambient (1995), Synaesthesia (1999) and Drunken Forest (2007).

Beyond her solo recordings, she has recorded or performed with Dave Douglas, Butch Morris, Kim Gordon, and many others, including as Hemophiliac, a trio with John Zorn and singer Mike Patton, as well as being a member of Zorn's Electric Masada. With Zeena Parkins, she records and tours as duo project Phantom Orchard. She often records on Tzadik, as well as designing the covers for many of their albums.

Mori has drawn inspiration from visual arts. Her 2000 release, One Hundred Aspects of the Moon was inspired by famed Japanese artist Yoshitoshi. Her 2005 recording, Myrninerest, is inspired by outsider artist Madge Gill.

In 2006, she was awarded a grant from the Foundation for Contemporary Arts Grants to Artists Award.