Following a stint in the short-lived Roosters with Eric Clapton, McGuiness joined the 1960s group Manfred Mann as a bassist, performing in a line up with Paul Jones. As the band sought to transform itself from jazz into a rhythm and blues orientated group, he took over bass duties from Dave Richmond and received joint songwriting credits on the group's early hits. Explaining how he came into the group, McGuiness said, "They had a great bass guitarist, but he was into Charles Mingus and things like that, which the whole band was. But he refused to play simple bass lines that would fit Bo Diddley numbers. He'd play incredible 3/4 lines and things like that. So I came in and I had the overwhelming advantage of not really being able to play the bass guitar, so I played simple." Appointed the writer of album sleeve notes, he took the opportunity to identify himself as "the nastiest in the group".
When Mike Vickers then Paul Jones left the band McGuinness started to take the role of guitarist and Jack Bruce played bass until replaced by Klaus Voormann. McGuinness' National Steel guitar became an important part of the group's sound and featured on hits such as "Pretty Flamingo". He composed a few album tracks for the group, notably the guitar instrumentals "L.S.D" and "One Way", also Mighty Garvey!'s surreal "Cubist Town".