U2 closed the show and for many the highlight of the night came when Clinton joined the band on stage for a special acoustic-version of 'Sunday Bloody Sunday' performed by Bono and The Edge, which moved the former president to tears.
Before performing the song, Bono paid tribute to Clinton's role in the Irish peace process.
“When Edge and I think of all the reasons we might want to be here in the Hollywood Bowl, the Clinton Foundation would be enough. But right on top of the list... is that we live in a country now that is largely and truly at peace -- north and south -- because of the intercession of the 43rd President of the United States, William Jefferson Clinton. He is by far the most beloved American since JFK for all of us Irish.”
The singer added: “I also want to salute the extraordinary brain he calls his missus... her patience and impatience in traumatized spots of the world is something we should all think of.”
After the duo finished their set, the former president wrapped his arms around both men.
“We've been friends for a long time,” Clinton told the audience. “And I want to say to Bono, thank you for the One Campaign. Thank you for campaigning against debt, thank you trying to save the foreign aid budget of the Secretary of State of the United States, thank you for campaigning against poverty.”
He added: “I want to say to Edge thank you for doing something very close to my heart. When Katrina almost destroyed the most unique, cultural and musical resource in America in New Orleans, this man led an effort to raise money for the all those musicians in New Orleans area who had no money but who are part of America's history and I will never forget it.”
Earlier in the night Lady Gaga had emerged from an all-white treehouse sporting a wavy blond hairdo and red lips like Marilyn Monroe, who famously crooned "Happy Birthday, Mr. President" to President John F. Kennedy in 1962.
Lady Gaga similarly serenaded Clinton and changed several of her lyrics to reference him, including swapping the title of "Bad Romance" for "Bill Romance."
"I thought, 'My God. I get Lady Gaga, and I will have a heart attack celebrating my 65th birthday," Clinton later said.
Clinton, who turned 65 on Aug 19 but celebrated his birthday at a posh Hollywood party on Friday night, sat between wife Hillary and daughter Chelsea in the front row throughout Saturday's event at the outdoor venue set against the Hollywood Hills. Other famous attendees included Maria Bello, Ashton Kutcher, Jason Segel, Ellen DeGeneres, Colin Farrell and Chevy Chase.
"I am the only person in history who got to be President and then had a post-presidential birthday party attended by both Lady Gaga and the Secretary of State," Clinton joked on stage. "I want to thank Hillary because we met 40 years ago this year. When I met her, she was already doing the kind of work you see here long before it was cool."
Ticket prices for "A Decade of Difference: A Concert Celebrating 10 Years of the William J. Clinton Foundation," which was streamed live on Yahoo.com, ranged from $50 to $550. Other performers included Motown legend Stevie Wonder, country star Kenny Chesney, Somali rapper K'Naan, Colombian crooner Juanes and R&B singer Usher.
Usher kicked off his performance with a take on Joe Cocker's rendition of the Beatles classic "With a Little Help From My Friends" before launching into his hits "Yeah" and "OMG." The R&B singer accidentally split his pant legs while dancing to reveal his bare left leg. The wardrobe malfunction didn't stop Usher, who continued with his routine, telling the crowd: "I work hard."
Clinton himself is no stranger to performing. The saxophone-playing politician memorably belted out "Heartbreak Hotel" when he visited Arsenio Hall's show during his 1992 presidential campaign. Clinton didn't pick up the instrument on Saturday night, despite a plea from Lady Gaga, who informed him: "I wish you were playing sax with me tonight, baby."