He formed The Blue Notes with Chris McGregor, Johnny Dyani, Nikele Moyake, Mongezi Feza and Dudu Pukwana, and emigrated to Europe with them in 1964, eventually settling in London, where he formed part of a South African exile community that made an important contribution to British jazz. He was a member of the Brotherhood of Breath, a big band comprising several South African exiles and leading musicians of the British free jazz scene in the seventies and is the founder of "Viva-La-Black" and the "The Dedication Orchestra."
His first album under his own name Spirits Rejoice on Ogun Records is considered a classic example of the combination of British and South-African players. In the early 1970s, Moholo was also member of the afro-rock band Assagai. he also founded the bands Viva La Black and The Dedication Orchestra. Moholo has played with many musicians, including Derek Bailey, Steve Lacy, Evan Parker, Enrico Rava, Roswell Rudd, Irène Schweizer, Cecil Taylor, John Tchicai, Archie Shepp, Peter Brötzmann, Mike Osborne, Keith Tippett,Elton Dean and Harry Miller. Moholo returned to South Africa in September 2005, performing with George Lewis at the UNYAZI Festival of Electronic Music in Johannesburg. He now goes under the name Louis Moholo-Moholo because the name is more ethnically authentic.