In the fan-captured video posted to YouTube, Chappelle reminisced about Mayer's 2004 guest appearance on his hit sketch comedy show.
"I had a sketch," Chappelle told the screaming concert-goers. "Don't be mad, it was called 'White People Dancing.' Me and my friend Neal [Brennan], who I wrote 'Chappelle's Show' with, read an article about you [John Mayer]. And he was hilarious in it. 'You should ask that guy to do that sketch.' And he did it. And he did it so well."
Chappelle then broke the news about Murphy, speaking publicly about it for the first time: "And today, I got some terrible news. My good friend Charlie Murphy passed away this morning and everybody in comedy is heartbroken. So, John, you are a sight for sore eyes."
He then thanked Mayer.
Chappelle was the latest comedian to speak out about Murphy following his death.
The Murphy family told ABC News in a statement on Wednesday, "Our hearts are heavy with the loss today of our son, brother, father, uncle and friend Charlie. Charlie filled our family with love and laughter, and there won’t be a day that goes by that his presence will not be missed."
Other comedians and actors took to social media to pay homage.
"RIP my friend Charlie Murphy," rapper Snoop Dogg wrote. Mike Epps posted a video of the two joking around, adding, "Throw back with my man #charliemurphy clownin."
Chris Rock added, "We just lost one of the funniest most real brothers of all time."