The annual award from the National Constitution Centre in the US honours leadership and vision in the pursuit of liberty of conscience or freedom from oppression, ignorance or deprivation.
Bono proves that "the office of citizen is the most important in the world", Constitution Centre president Joseph Torsella said on Thursday.
Bono, 47, co-founded the organisation DATA (Debt, AIDS, Trade, Africa) in 2002 to work against the poverty and disease that plague developing nations, especially nations in Africa.
The Irish-born singer and his band U2 helped organise the Live 8 concerts in 2005, which called attention to debt in African nations. Bono has also used his celebrity status to put pressure on world leaders to do something about Aids and poverty.
Bono and DATA will receive the medal and a $100,000 prize at a ceremony on 27 September.
After the prize was announced, Bono issued a statement highlighting the 2.4 million Americans who pledged to help eradicate Aids through the ONE campaign.
"I don't suppose there are enough Liberty Medals to go around, but in truth, those people should all be wearing one, too," he said.
Last year, former presidents Bill Clinton and George Bush senior won the medal for raising more than $1bn for disaster relief after Hurricane Katrina and the 2004 tsunami in southeast Asia.