BONO has been awarded the first George W. Bush Medal for Distinguished Leadership by the former US President.
In a ceremony at the George W. Bush Presidential Center in Dallas, the U2 frontman was presented with the award in recognition of his work combatting the HIV/AIDS crisis and poverty in Africa.
The medal will be presented annually for individuals who have changed the world in a positive way.
In 2002, Bono convinced then-president Mr Bush to set up the President's Emergency Plan for AIDS Relief (PEPFAR) to battle against the spread of AIDS in third world countries.
"It's a huge honour to win this award, and I'm here to honor your leadership on the greatest health intervention in the history of medicine," Bono told Bush during the live-streamed ceremony in Dallas.
"That's what I'm not sure people understand - 13 million from PEPFAR, and if you add the Global Relief Fund, it's probably been 21 million lives have been saved by this work that you began and led and I'm here to honour that."
Bush replied: "The truth of the matter is, PEPFAR never would have made it out of Congress had you not been engaged. The first time I met you, you knew more statistics, like you were coming right out of the CIA.
"Here's the thing about Bono that people should understand - I like to say he's a real deal.
"This is a guy who has got a huge heart, obviously a talent, but cares so much about the human condition that he spends an enormous amount of time and capital on saving lives."
Bono also expressed his condolences to the former president following the death of his mother, the former first lady Barbara Bush, earlier this week.
He described her as "the mother of PEPFAR," for her role in helping to destigmatise AIDS - which included holding a baby with HIV and embracing a man with AIDS.
The Irish rocker and the ex-president have struck up an unlikely friendship over the past decade.
Last year, Bush posted a picture of himself with Bono at his Texan ranch, along with the cheeky caption: "Bono is the real deal. He has a huge heart and a selfless soul, not to mention a decent voice".
Speaking after receiving his award, Bono recalled: "I remember riding in his motorcade with George and people were waving, and I said, "Oh, Mr. President, you're very popular, clearly" and he just goes, totally deadpan, 'When I first came here, the people used to wave at me with one finger' and that made me laugh.
"I get it. You know, I might've been one of them."
Bono joked that he was worried he would be fired from U2 over the award, since his band mates were in Montreal rehearsing for their upcoming tour while he was being honoured by a former president.
He laughed: "I kind of snuck out the back window!"