Hollywood stars and the world's paparazzi have already begun arriving for the nuptials of the world's most sought-after catch, who will, sources said, celebrate with 136 guests at the exclusive seven-star hotel in the 450-year-old Palazzo Papadopoli.
The pair are expected to be officially married in a civil ceremony on Monday, but the city of masks is preparing for a weekend of serious partying before then.
"Clooney's on everyone's lips here in Venice, the girls in particular are all in a tizzy, they'll be lining the banks of the canal to see him," said watertaxi driver Bruno Bartolini, who said iwould be "a fantastic party."
"The city's ground to a halt because they're using the grand canal, but what does that matter: there's nothing better than getting married in Venice," Bartolini said.
Though the world's most famous waterway will not be closed entirely, there were grumbles in the northern Italian city over the disruption caused by the wedding and such an ostentatious display of wealth in times of economic crisis.
"Clooney's not bringing us bread for our tables, his getting married here will do nothing to better our problems," said 16-year-old Viviana, who slammed him for "coming here with all his nice money while we can't find jobs."
Fellow local resident Silvana agreed, saying: "It would have been better for all of us if he'd gone to get married in some secret countryside location."
But nothing appears able to dampen the spirits of the crowds of tourists eagerly snapping photographs of the town hall and Aman from the water ferries, or the locals staking out the best viewing positions in houses along the canal.
All desperate for a glimpse of the erstwhile bachelor in his Armani suit and Alamuddin in an Alexander McQueen creation designed by Sarah Burton, the woman behind the gown worn by Britain's Kate Middleton at her wedding to Prince William in 2011.
Alamuddin, who moved to Britain with her family as a three-year-old, is a top human rights lawyer who met the Hollywood star through his humanitarian work.
Guests including Brad Pitt, Angelina Jolie, Sandra Bullock and Matt Damon are set to stay at the Hotel Cipriano on the island of Giudecca, where they are expected to dine in style Friday evening with the groom and his glamorous bride-to-be.
The reception will take place on Saturday at the luxurious waterfront Aman, where guests will be escorted by police boats keen to keep over-excited Clooney admirers and hundreds of photographers at a distance.
They'll be met with lashings of fizz and canapes in the garden, an oasis sheltered from the bustle of the canal, before sitting down in the main library to a sumptuous five-course dinner rustled up by a renowned Italian chef, according to a source close to the hotel.
The Aman's restaurant will be then transformed into a nightclub, where they'll dance the night away, a source said.
The singer Lana Del Rey is reported to be preparing to serenade 53-year-old Clooney and Alamuddin, 36.
Speed boats will be banned from stopping in front of the hotel to keep goggling to a minimum.
Rome's former mayor Walter Veltroni, a long-term friend of Clooney's, will be performing the civil ceremony, which is likely to be held in the town hall, the stunning Ca' Farsetti 14th century palace opposite the Aman hotel.
The streets around the town hall will be off limits to the public from 12 noon (1000 GMT) for two hours on Monday, when the ceremony is expected to take place.