The international name is the latest high-end retailer to move into the former GPO building in Ingram Street.
The news came a week after the Evening Times revealed a planning application had been made for a Hard Rock Cafe at the Athenaeum in Buchanan Street and there are plans in place to designate the area around Renfrew Street, the North Quarter.
The German fashion house, which is worn by celebrities including Ryan Reynolds and Sienna Miller, will open its new flagship store in the former GPO Building in Ingram Street this summer.
It will take over the former All Saints store and the vacant unit behind it in South Frederick Street to transform it into an emporium selling clothes and accessories.
The brand follows in the footsteps of luxury shops and restaurants, including Jamie's Italian, Cruise, Agent Provocateur and Jaeger, cementing the area's status as a designer junction.
On the same block, Ralph Lauren recently agreed to a lease extension on its store – its only stand alone store outside London – until August 2022.
Isla Monteith, of Cushman and Wakefield, who acted on behalf of landlord Henderson Global Investors to secure the 10-year lease, said: "It really does emphasise how important Glasgow is for shopping. Outside of London it's the city luxury names want to buy into.
"Other places are seeing shops shy away from investing but this part of Glasgow in particular is thriving."
The store will take over around 7737sq ft over ground floor and basement levels.
Hugo Boss will also keep its smaller store in Buchanan Street open.
Isla said the success of Glasgow's designer district is down to shoppers moving towards buying quality rather than quantity.
She said: "People want to buy investment pieces that will last them more than just a season. The new store is moving into the heart of the city's retailing destination."
Councillor Gordon Matheson, leader of Glasgow City Council and chair of the City Marketing Bureau, said: "This latest endorsement from Hugo Boss not only continues Glasgow's enviable association with such a world-famous fashion brand but will also breathe new life into the GPO building."