For the last two years, the old St Andrew House building in West Nile Street has been transformed into a budget hotel.
The new Premier Inn has 210 bedrooms and views of the city from the top of the 18-storey tower, making it the tallest branch of the company in Scotland.
The hotel will be the fifth General Manager Brian Halfpenny will oversee in the city, bringing the total rooms of the chain to more than 2000.
He said: "The conversion has been fabulous.
"We've got a lot of diverse properties, but this will be our flagship one.
"We're on the Style Mile so it's important to us that the hotel is very visual and fits in.
"There's a wee joke with the other hoteliers that I'm 'King of the City' as I'm the biggest bedroom provider in Glasgow.
"Premier Inn sees more mileage in Glasgow, especially with Glasgow 2014 coming up.
"A lot of stuff is going on and we're here on the back of that and hoping we can deliver."
The development comes as part of Glasgow's ongoing focus on major infrastructure developments in preparation for the Commonwealth Games.
There are now more than 9000 hotel bedrooms within a 10-mile radius of Glasgow city centre with more than 1100 hotel rooms and luxury serviced apartments being built between now and 2014.
Scott Taylor, Chief Executive of Glasgow City Marketing Bureau, said: "Glasgow returns a hotel investment at an impressive level. And with the Commonwealth Games less than two years away investors know that Glasgow is a safe bet, which is why they're pressing ahead with plans to open really great new hotels, like the new Premier Inn.
"This important addition to our burgeoning hotel scene will further increase the city's attractiveness to tourists and takes us one step closer to fulfilling the infrastructure needs of major conference and event organisers, reinforcing Glasgow's competitive edge."
The St Andrew House building was built in 1962 and was one of the city centre's first high rise office blocks, but has become a notorious eyesore in recent years.
Whitbread Hotels, the owners of the Premier Inn chain, bought the derelict building in 2008 and began construction in 2010.
Designed by Ryder Architecture and built by construction company Mansell, the scheme was undertaken on behalf of West Nile Construction and has since been entered in the 2012 Glasgow Institute of Architects awards.
It has also brought 70 new jobs in partnership with employment specialists Working Links.
Half of the jobs were filled by people on its Work Programme which involves hiring young people not in employment, education or training.
This is something Brian Halfpenny hopes will help him retain more staff, something uncommon in the hospitality industry.
He added: "We are giving people the opportunity to get their first start on the job ladder, and it will be fantastic to watch them progress in their career."
Operations manager Vivienne Carr started with the company as a waitress five and a half years ago and has worked her way up to her present position in the West Nile Street branch.
Vivienne, who lives in the city centre, said: "I'm so excited to start. It's been a long process and we're all eager for our families and friends to come and see it."