The 69-year-old former Beatles rocker and other guests were treated to two hours of performers, putting their own twist on tracks from his back catalogue.
Coldplay performed 'We Can Work It Out', while Katy took to the stage to sing 'Hey Jude' and Neil Young and Crazy Horse gave a rendition of 'I Saw Her Standing There'.
Meanwhile, Foo Fighters covered Wings track 'Jet' and frontman Dave Grohol admitted it had been tough trying to decide what to perform.
He told The Hollywood Reporter: "Paul's rock songs are what the Foo Fighters have always aspired to be - uptempo, melodic, catchy beautiful rock songs. There are plenty of those to choose from in Paul's catalogue."
Paul also performed at the 22nd annual event, held in Los Angeles on Friday (10.02.12) joining Cirque Du Soleil early in the evening for 'Magical Mystery Tour'.
He returned later to perform two tracks from his new album. 'Kisses on the Bottom': 'I'm Gonna Sit Right Down And Write Myself a Letter' and 'My Valentine', as well as a medley of 'Golden Slumbers', 'Carry That Weight' and 'The End', which featured Dave and Joe Walsh on guitar.
Paul was honoured by MusiCares for both his music and extensive philanthropic efforts, including animal rights and environmental protection work.
The evening raised over $6 million for the charity.