Bono gave a funky, rousing introduction to Wonder, who headlined the second annual concert. Wonder wowed audience members, who danced and sang along to songs including "Superstition" and "Isn't She Lovely."
"This is a global celebration," Wonder yelled to the crowd. "We will end extreme world poverty in our lifetime."
Wonder has been a United Nations Messenger of Peace with a special focus on disabilities since 2009. Messengers have recognized talents in the arts, academia and sports and help bring attention to U.N. work.
The Global Citizen Festival coincides with the U.N. General Assembly. Fans earned free tickets for helping spread the word or volunteering to help end world poverty. World leaders who attended included Secretary-General Ban Ki-moon and Liberian President Ellen Johnson Sirleaf.
"There is so much energy here tonight. We can power the world," Ban told the crowd.
Will.i.am and Olivia Wilde were among the celebrity attendees.
Wonder ended the five-hour event, electrifying the crowd during his hourlong performance. He even teased concertgoers before singing "Signed, Sealed, Delivered I'm Yours."
"That's it!" he yelled, then added: "Y'all wanna jam some more?"
John Mayer also performed Saturday and was a favorite with his solo work on the guitar. He was full of power when he performed "Slow Dancing In a Burning Room" and "Gravity."
"It's so nice to be here," he said.
Other performers included Kings of Leon and Alicia Keys, whose set included "No One" and "Empire State of Mind."
"I believe if we don't care about each other, who will?" the singer said. "Help me celebrate tonight so we never forget."
Wonder also had a touching moment when he sang John Lennon's "Imagine" and encouraged the audience to lobby for more gun laws.
"Can you believe blind people have guns?" he said. "Let's keep it real. Ridiculous."
Last year's Global Citizen Festival featured Neil Young and Crazy Horse, Foo Fighters and The Black Keys. The festival's nonprofit partners pledged $1.3 billion in new fundraising commitments last year.
Wonder, who played the piano and harmonica, was joined onstage by R&B singers Maxwell and Janelle Monae.
"I can't believe this is happening," Maxwell gushed when singing "Superstition."