In the early 1960s, Collins, drummer Jimmy Carl Black and bassist Roy Estrada joined with Frank Zappa to form the Soul Giants which, under Zappa's leadership, turned into the Mothers of Invention. Collins was the lead vocalist on the Mothers early albums, including Freak Out!, Absolutely Free and Cruising with Ruben & the Jets.

He contributed to other Zappa projects through the mid-1970s.