"I've never done anything like this in my life before," said Clapton during Thursday's concert, which saw the Rock and Hall of Famer use his guitar skills to play jazz classics like "Joe Turner's Blues," "Corrine, Corrina" and "Ice Cream."
An admittedly nervous Clapton revealed that his love of jazz music went back to his childhood.
"I wanted to be in a jazz band as a kid, but the guitar took me away," he told the audience.
But for one night, at least, he was the star of one, running through songs he'd selected - and one that he didn't.
"Here's a song that I didn't really want to do," said Clapton. "I said the only way I'll do it is if Wynton would make it sound like it came out of New Orleans."
Clapton and company then launched into a sultry, jazzed-up version of his classic "Layla," complete with trumpets, a trombone and a clarinet.
Marsalis praised Clapton for not only donating his time for the event, which raised $3.6 million, but also for his deep knowledge of the genre.
"The depth of respect I have for this man...," said Marsalis as he lauded Clapton, adding that it was an honor to play with the rock god.
"So much is not what it's said to be," Marsalis said. "This man is for real."
The concert also featured a guest appearance from musical great Taj Mahal.
