It is the third wedding for Hollywood star Cruise
The wedding was celebrated by a Scientology minister in accordance with the couple's faith and attended by a host of show business stars.
Crowds of onlookers and journalists gathered outside the Odescalchi castle in Bracciano, just north of Rome, for a glimpse of the celebrities.
The wedding capped a week of Hollywood mania and media frenzy in the town.
The centre of Bracciano was sealed off from Friday night and extra police brought in.
As darkness fell, oil-fed torches glowed from the battlements of the 15th Century castle, which rises above the town on the shores of Lake Bracciano.
The guest list included fellow Hollywood stars Jennifer Lopez, Will Smith and his wife Jada Pinkett Smith, Jim Carrey, and Richard Gere.
Holmes wore a Giorgio Armani dress, with an ivory train adorned with lace and crystal embroidery, while Cruise wore an Armani tuxedo, reports said.
After the ceremony, the couple were serenaded by Italian singer Andrea Bocelli.
Holmes and their seven-month-old daughter, Suri, arrived at the castle earlier in the day, followed by Cruise.
Cruise, 44, and Holmes, 27, got engaged in June 2005, two months after they were first photographed together in Rome.
Cruise, who has starred in Mission Impossible and War of The Worlds, said he proposed to Holmes on top of the Eiffel Tower in Paris.
It is Cruise's third wedding. He was previously married to actresses Mimi Rogers and Nicole Kidman.
He adopted children with Kidman before they divorced in 2001.
The Church of Scientology was set up in the US in 1954 and claims eight million members worldwide.
The church's teachings are based on the writings of the late science-fiction author L Ron Hubbard, who spelled out principles that he called Scientology and Dianetics.
But critics say it is a fake religion based on making money from its followers.
A Scientology wedding contains many elements familiar to traditional marriage ceremonies, including rings and wedding vows.
But it also includes certain elements fundamental to Scientology, such as vowing never to go to bed without talking about any differences.A spokesman for the Church of Scientology said its wedding ceremonies are not legally recognised in Italy, so Cruise and Holmes would also have to have a civil union.