With her late husband, John Lennon, the couple sparked a generation of celebrity campaigning with their 1969 "Bed-In" honeymoon as a demonstration against the Vietnam War and in favour of world peace.
From Live Aid, Band Aid and even Farm Aid in the 1980s, to Bono's tour of Africa with US Treasury Secretary Paul O'Neill earlier this decade, pop-star involvement in everything from politics to poverty reduction is ubiquitous.
But it wasn't always that way.
"When John and I were sort of talking about world peace and love and all that kind of thing, bed-ins and so on, you know, people were just laughing at us," Ono said.
"But now I think everybody is involved because we just know that we have to do something about this world."
Ono has teamed up with Hard Rock International for an "Imagine There's No Hunger" campaign.
As was the case with her earlier initiatives, music is central, including a song by Lennon, but its use has evolved to accommodate the online generation.
The campaign, which will raise money for non-profit, anti-poverty group World Hunger Year, harkens back to Lennon's 1971 ballad Imagine.
To raise money for WHY, it is releasing an album, called SERV4, for download.
The album costs $12 (R89), with the songs selling for $0.99 each. It will be available through the Hard Rock cafes, hotels and the WHY website with downloads also obtainable from iTunes and Amazon.
Rock group OAR is donating a live track of its song, Lay Down, to the digital album, which will also include Lennon's Gimme Some Truth.
It will also feature versions of rare, live or previously unreleased tracks from Elvis Costello, Eric Hutchinson, Brett Dennen and others.
Ono says she finds hunger a particularly poignant issue due to her own childhood.
"During World War Two, I was in Japan, and as kids, we were evacuated to the countryside . All the city kids were starving," she said.
"I remember that feeling and it's very unpleasant. It's just a cruel thing to do to kids."
It doesn't matter whether the new generation of activist celebrities harkens back to Lennon and Ono's legacy, she says.
"They don't have to necessarily think that it was our legacy or something like that," Ono says.
"Let them to do what they think they can do. It's very important, instead of sort of towering over them and saying, 'We did it'."
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