The 200,000-square-foot unit is the anchor store of the newly opened Victoria Square retail complex in the center of town. Other tenants in the 800,000-square-foot complex include H&M, French Connection and Reiss.
Victoria Square is widely seen as a major player in the city's revival, after the Good Friday peace agreement was signed in 1998 with the aim of putting an end to sectarian violence in the region.
"I think the people of Belfast will be blown away," said John King, chief executive of House of Fraser during a walk-through with press and colleagues from House of Fraser.
"This is the first store opening since House of Fraser was bought by [The Highland Group, a consortium led by Icelandic investment group Baugur Group], and shows our new ideas," said King. "Our view has always been that we wanted to offer access to premium brands which, previously, shoppers here would have had to go to Glasgow or elsewhere for."
The store is decked with shiny white walls and floors, which contrast with mirrored and black vinyl panels on the shop's units.
The company has upped the store's premium brand content, with shop-in-shop units including an Anya Hindmarch concession with mirrored, Art Deco fixtures and an Agent Provocateur shop-in-shop, along with Aquascutum and Mulberry concessions.
To further bolster House of Fraser's image, the company has signed model Yasmin Le Bon as its face for spring. She was on hand in Belfast to cut the store's opening ribbon.
The Highland Group purchased House of Fraser for 351 million pounds, or $706 million at current exchange rates, in 2006.
And while consumer spending may have slowed in Europe in recent months, Colin Porter, commercial director of House of Fraser, said the retailer had no concerns about opening its largest and most high-end store at difficult trading times.
"When times are tough, people either shop up or shop down," said Porter. "We want to focus on customer service, the customer being a guest and creating a memorable experience."