"Now we're gonna rock it up," Richards said before launching into "Sweet Little Rock N' Roller."
Richards' appearance was only the beginning of Clapton's hour-plus-long set, which included hits like "Crossroads" and "Little Queen of Spades." It also featured other special guests, like Robbie Robertson, who sang the classic "I Shall Be Released."
"I just want to say it's an honor to be here in honor of Crossroads and Eric Clapton," Robertson said.
Crossroads Guitar Festival, which benefits Clapton's Crossroads Centre for substance abuse in Antigua, has been held every three years since 2004; this Friday and Saturday was its first at Madison Square Garden.
The show lasted almost five hours, with each performer showcasing his particular brand of wizardry on the instrument. (All the headliners were men, though there were a few women as supporting players in the program.)
Clapton joined Los Lobos and Robert Cray early on, and Warren Haynes and Derek Trucks played an acoustic set and brought out Gregg Allman. Keb' Mo' and Taj Mahal paid tribute to the blues in their acoustic set, while newcomer Gary Clark Jr. had the crowd on its feet throughout most of his electrifying set, which was followed by another fiery set, this one by Jeff Beck.
Other highlights were a performance by blues great Buddy Guy and a set from Vince Gill, Keith Urban and Albert Lee.
"It's one of the greatest things that ever happened, getting this invitation from Eric Clapton," Gill gushed onstage.
The night ended with just about all the evening's performers coming back on stage for a jam session with Clapton.
"See you in three years," Clapton told the crowd before exiting the stage.