"There is a sense of loss not just amongst the firefighters but I am sure the citizens of Glasgow".
The Mackintosh building had been due to re-open next year after millions of pounds in restoration works following a May 2014 fire.
Scottish Fire and Rescue Service (SFRS), who were still working to extinguish the flames on Saturday morning, said no-one was killed or injured in the incident.
There were no casualties, the fire service said. "My first thoughts tonight are for the safety of people - but my heart also breaks for Glasgow's beloved [School of Art]".
A huge fire devastated a historic building in Glasgow, Scotland, overnight.
"It's hard really to say much until there's an evaluation or report on the building".
The rear elevation of the Glasgow School of Art is seen on fire, in Glasgow, Scotland, Britain, June 15, 2018, in this still image obtained from social media.
Alan Dunlop, professor of architecture at te Glasgow School told The Guardian, "The building does look as though from the inside it's been totally gutted".
By morning the fire was under control, but smoke was still rising from the building as firefighters sprayed it from tall ladders.
A number of roads around the art school were closed while crews tackle the blaze.
A restoration project, set to cost between £20 million and £35 million ($26.5 million and $46.5 million; 23 and 40 million euros), had been returning the world-renowned institution to its former glory following a fire in 2014.
Paul Sweeney, shadow Scotland minister, said the Mackintosh Building was the "most architecturally important building" in the city.
Calling it "severe and extensive", she said it's too early to tell whether the building can be restored again, noting that structural assessments are underway now, the Guardian reported.
The UK government "stands ready to help, financially or otherwise", he added.
In recent years, the school has produced numerous UK's leading contemporary artists such as Douglas Gordon, David Shrigley, and three recent Turner Prize winners: Simon Starling in 2005, Richard Wright in 2009 and Martin Boyce in 2011.
The fire in 2014, caused by a faulty projector, destroyed the building's library, which was recognised as being one of the finest examples of art nouveau in the world.