Lynton Lasers from Manchester will use infra-red machines to remove dirt from the priceless artworks in and around St Peter's Basilica.
Many of the pieces on display in Rome need restoration after being untouched for centuries and facing damage from a build-up of dirt and pollution damage.
The technology, which is used to remove tattoos, will leave the artwork looking as good as new, experts say.
The company has said it will leave one of its laser machines in the Vatican so it can clean on a more regular basis.
Chairman Andy Charlton told the Manchester Evening News: "With artwork or frescoes it can be done but it's more difficult when you're dealing with pigment.
"The light heats up the dirt and blasts it off, but you want it to be self-limiting, so it doesn't also heat up the paint underneath.
"It's similar with a tattoo, apart from the ink is in the skin - you want to blast that away without damaging the skin."