The nine-storey development will have more than 370 bedrooms and a distinct glass shape. It will tower above the River Clyde, sitting on the corner of Oswald Street and Argyle Street.
The site, near Central Station and the International Financial Services District, was to have been a new office and retail development by Buccleuch Property.
Instead, the firm has agreed a deal with German hotel chain Motel One, which already has a hotel near Waverley Station, Edinburgh.
Building work will start next year and the hotel - described as "budget boutique" - will also have a car park.
It is expected to be fully operational by the summer of 2015. Planning approval has already been granted by Glasgow City Council.
Sandy Smith, of Buccleuch Property, said: "The deal with Motel One is an extremely positive one for Glasgow. Its development will continue to encourage economic development in the city, creating hundreds of construction jobs, as well as others when the hotel opens.
"Having secured planning permission on the site for an office and retail scheme back in 2007, we put our proposals for developing it on hold during the economic downturn.
"During this time we were approached by a number of parties interested in the site.
"Motel One proved to be a good fit. Working closely with the company and Glasgow City Council, we agreed a deal for alternative use, which the International Financial Services District and the city planners have been highly supportive of."
Motel One has 45 hotels and almost 10,000 rooms in Germany, Austria and Scotland, with others under construction in Belgium.
A spokesman for Glasgow City Marketing Bureau said: "Motel One's decision to open shows that international developers continue to recognise the city's distinct market advantages and will further strengthen its competitive edge."
The hotel will be the largest north of the border and once completed Glasgow will be able to proudly boast of having Scotland's two largest hotels - both within walking distance of each other.
Jury's Inn Glasgow is in nearby Jamaica Street and currently holds the crown with 321 rooms. But Motel One will offer at least another 50 rooms when it opens.