The singer was dared to undertake the stunt by fellow Voice UK coach Jessie J, who shaved her head to raise money for the charity initiative.
In a video filmed on the set of The Voice, the 'Price Tag' singer and presenter Holly Willoughby can be seen warming wax strips in their hands before sticking them to O'Donoghue.
"I've never had this done before, though people would swear otherwise," he admitted. "I'm really nervous - does it hurt?"
"It kills," replied Willoughby.
Tom Jones - who is seen watching on while sporting one of the charity's red noses - can then be seen counting down from five, before the strips are simultaneously ripped off.
O'Donoghue cries out in pain, but manages to hold back from swearing, instead shouting: "Voice UK."
"Look at that!" said Jessie J, as she showed the hair-covered strip to the camera. "Boyband material."
After deciding that they needed to remove the remaining strip of hair in the centre of the singer's chest, host Reggie Yates can be seen pulling a third and final strip off.
This year's live Comic Relief fundraiser is airing on BBC One tonight (March 15).
As well as Jessie J's head-shaving stunt, the show includes the return of Ricky Gervais as his Office character David Brent, and a special episode of The Vicar of Dibley.