Cadogan Street in the heart of the financial district was closed off after smoke could be seen billowing across the skyline.
Fire fighters were dispatched to the area near Central station after the alarm was raised at 8.50am.
The derelict building was already scheduled for demolition. There are no reports of injuries.
A spokesperson for the Scottish Fire & Rescue service said: “We received multiple calls of reports of a building fire on Cadogan Street in Glasgow at 8.50am.
“Four units were dispatched to investigate and we remain on the scene.”
Police closed the road off while fire crews tackled the flames in the derelict building.
A spokesperson for the force said: “We were called to assist the fire bridge with a building fire on Cadogan Street in Glasgow at 9am this morning.