The campaign Digital Life Sacrifice will raise money on Wednesday - World Aids Day - for Keep a Child Alive, which supports families affected by HIV/Aids in Africa and India.
The celebrities have filmed "last tweet and testament" videos.
They will sign back online when the charity raises $1 million.
Their videos will appear in adverts showing them lying in coffins to represent what the campaign calls their digital deaths.
Lady Gaga is hugely popular on Facebook with nearly 24 million fans, plus more than seven million followers on Twitter.
Grammy-winning singer Keys, 29, said it was "really important and super-cool to use mediums that we naturally are on".
"It's so important to shock you to the point of waking up," the R&B singer said. "It's not that people don't care or it's not that people don't want to do something, it's that they never thought of it quite like that."
The campaign also includes Elijah Wood, Jennifer Hudson, Ryan Seacrest, Kim and Khloe Kardashian, Serena Williams and Keys' husband, rapper-producer Swizz Beatz.
"This is such a direct and instantly emotional way and a little sarcastic, you know, of a way to get people to pay attention," said Keys, who has more than 2.6 million followers on Twitter.
Leigh Blake, the president and co-founder of Keep a Child Alive, said: "We're trying to sort of make the remark: 'Why do we care so much about the death of one celebrity as opposed to millions and millions of people dying in the place that we're all from?'"
He added that he thought Lady Gaga would raise the money "all by herself".
"She's got a very, very mobilised fan base and that's beautiful to watch I think (and) she's able to draw their attention to these issues that are very important, you know, and that people follow it and act."
Celebrity requests accepted
Keys, who gave birth to her son Egypt last month, said recruiting celebrities was difficult because of scheduling, but "once I got people on the phone and I was able to paint the concept for them, everybody was in".
Keys, who gave birth to her son Egypt last month, said recruiting celebrities was difficult because of scheduling, but "once I got people on the phone and I was able to paint the concept for them, everybody was in".
She added that no-one refused her request.
Keys is hoping more people, not just famous names, will get involved in the initiative.
"It just doesn't have to be just because you're a celebrity or something like that. It can be anybody."
She added that being mother and wife made her want to help others even more.
"As a human being, you deserve to have a chance at life," she said.
Source: BBC Entertainment