Michael Stipe performs with Bono at the event
The first annual Love Rocks concert paid tribute to the Irishman's "outspoken philanthropy", and raised money for research into heart disease.
Singer Lauryn Hill, actor Sean Penn and comedian Drew Carey joined Disney chairman Michael Eisner at the event, which saw Bono awarded the Heart of Entertainment award.
Tom Cruise told the audience at the Kodak Theater - which hosts the Oscars next month - that Bono "makes us all proud to be human".
Debt relief
Bono, whose real name is Paul Hewson, has championed causes such as debt relief and Aids awareness in the developing world.
He has also put his weight behind campaigning groups including Amnesty International and Greenpeace.
REM performed a set which included a cover of I've Got You Babe, which saw Cher make a surprise appearance to duet with Michael Stipe - the first time she had performed it without her late husband Sonny Bono.
Later, the band also performed U2's One with help from Bono on vocals, and Stipe paid tribute to him as "a singer, songwriter, statesman, and fashion plate".
'Thorn'
Accepting his award, Bono described himself as a "thorn in the shoe" of George W Bush's administration, and warned of the threat Aids poses to the people of sub-Saharan Africa.
"This is probably the greatest threat to humanity that the world has seen really since the bubonic plague took out a third of Europe in the Middle Ages," he said, adding 100 million children could be orphaned because of the epidemic.
Video tributes were also sent by former US president Bill Clinton and Rolling Stones singer Mick Jagger.