Born in 1950, Rother went to school in Munich, Wilmslow (England), Karachi, and Düsseldorf. He also lived in Pakistan in the early 1960s where he was exposed to Pakistani music that would influence his own music in the late 60s and early 70s. From 1965 Rother played in the band Spirits of Sound, from which other members would later go on to join Kraftwerk and Wunderbar.
Rother is a multi-instrumentalist (primarily guitar and keyboards) who, along with a catalog of several solo albums starting in 1977, is best known for having co-founded the German group Neu! with drummer Klaus Dinger (five albums between 1971 and 1996), and his collaborative efforts with Hans-Joachim Roedelius and Dieter Moebius (aka Cluster) under the name Harmonia (two albums, one in 1974 and 1975, with later 1976 sessions recorded with Brian Eno; the studio tapes for the latter disappeared but were found by Roedelius two decades later; he remixed the tapes and released the results as Tracks and Traces in 1997; Rother was the main producer for the version re-released in 2009). Rother and Dinger were also in a short-lived version of Kraftwerk in 1971, with Florian Schneider, during a time when founding member Ralf Hütter had temporarily left the band. (This version of the group was filmed during an appearance on the German music show Beat Club, which has been available sporadically on VHS and DVD.)
Beginning in the late 1970s, Rother began issuing LPs under his own name: Flammende Herzen (1977), Sterntaler (1978), and Katzenmusik (1979) all featured drums by Can percussionist Jaki Liebezeit. Further releases included Fernwärme (1982), Lust (1983), Süssherz und Tiefenschärfe (1985) and Traumreisen (1987). Rother regained the rights to these releases in the late 90s, and re-released CD versions of them, all of which contained bonus tracks, usually in the form of then-current remixes of original album tracks. Along with these reissues were a best-of compilation, Radio, and a new release, Esperanza (1996). His most recent album; Remember (The Great Adventure) featured vocals (a first for Rother's solo work) and was released in 2004.
On 1 July 2007 Michael Rother joined the Red Hot Chili Peppers for a live jam at the end of their concert in Hamburg. Together they played for nearly 25 minutes in front of 35,000 people. In November 2007 he toured with Dieter Moebius (another member of Harmonia) as Rother & Moebius. On 27 November 2007, a Harmonia reunion concert was announced for Berlin, where they performed together live for the first time since 1976.
In 2010, Rother played five shows in Europe with Sonic Youth drummer Steve Shelley and Tall Firs guitarist Aaron Mullan (who played bass in the trio). This group, known as Hallogallo, performed the music of Neu! live for the first time in many years. They also played the ATP New York 2010 music festival in Monticello, New York and Incubate 2010 in Tilburg, Netherlands in September 2010. In November 2013, Rother will perform the music of Neu! and Harmonia at the final holiday camp edition of the world famous All Tomorrow's Parties festival in Camber Sands, England. 
The discography of Michael Rother consists of nine studio albums, two compilations and seven singles.
As a member of Neu! Rother released three studio albums, two albums of studio out-takes (Neu! 4/Neu! '86) and rehearsal recording. As a member of Harmonia, Rother released two studio albums, one live album, a studio out-takes album and a remix album. In 2010 Rother released the "Blinkgürtel" single with his live group Hallogallo 2010.