The group — which includes British comedian Jack Dee and Spice Girl Mel C — will make the five-day journey up the African river in dugout boats, canoes, and white water rafts.
The journey, which it is hoped will raise £1m, (€1.18m) is being staged ahead of this year’s Red Nose Day on Mar 15.
The celebrities will face rapids known as Gnashing Jaws of Death, the Washing Machine, and Oblivion, on their way to the world’s largest waterfall, Victoria Falls.
Ó Briain said: “When I was first asked to do this challenge, I did a quick Google search of Zambezi rafting but after the tenth page of people being instantly flung into the water I turned off the computer.
“But lives can be changed if people put their hands in their pockets in exchange for our misery so that sounds like a fair deal.”
Mel C, who released a single for the charity with the Spice Girls in 1997, said: “It’s going to be tough.
“It’s going to be physically and emotionally demanding, but we’ve all got each other and hopefully we’ll be able to get through it.”
The group has already been put through its paces with training at the Lee Valley White Water Centre, used as the canoeing venue for London 2012.
Dee said: “It was an important day of training to get us ready for being on the Zambezi. Whether it’s actually accurate I don’t know. I have a sense that it’s probably like having a go on the dodgems in order to go and do Formula One at Monaco. I suspect the difference is going to be fairly considerable.”
The proceeds will be used to help educate children in Zambia.