A policeman reportedly told pedestrians in the area that there is asbestos in the smoke following the fire which broke out on Thursday morning on Sauchiehall Street at the junction with Hope Street.
A number of properties have been evacuated and over 100 firefighters are still tackling the blaze.
Emergency services were called to the scene at 8.18am on Thursday after a blaze took hold in the roof space of commercial premises.
Smoke billowed across Sauchiehall Street and streets were cordoned off as fire crews battled the blaze.
The Scottish Fire and Rescue Service (SFRS) said the occupants of several nearby properties were evacuated and there were no reports of any injuries.
Hope Street was closed to all traffic between Bath Street and Renfrew Street, with Renfield Street also closed between Renfrew Street and Bath Street while emergency services dealt with the incident.
An SFRS spokesman said: “The Scottish Fire and Rescue Service was alerted at 8.18am to reports of a well-developed fire which had taken hold within the roof space of a commercial premises.
“Operations control mobilised a number of fire engines to Sauchiehall Street, Glasgow, where firefighters are currently on the scene working to extinguish the fire.
“Crews have safely evacuated the occupants of several nearby properties.”
Assistant Chief Officer Lewis Ramsay said: “This is an extremely challenging incident but the response and professionalism of our firefighters has been outstanding.
“We would urge the occupants of surrounding buildings to remain indoors and keep their windows closed due to the suspected presence of asbestos.
“This will be a protracted incident and crews will remain on the scene as they work to prevent further fire spread and damage in this prominent city-centre location.”
Firefighters were also spotted gaining entry to the nearby Pavilion Theatre.
Iain Gordon, general manager of the theatre, said: “It’s getting worse, the flames are leaping out of the top now.
“Everybody is out of the area, they have all been evacuated.
“Our problem at the moment will be smoke damage because it’s gone right into the side of the building.
“We are very concerned about everything. The building has been there for a long time and is a major part of Glasgow.
“When you see how quickly the fire spread to other parts of the buildings in Sauchiehall Street we just hope the flames don’t jump across the lane.
“It’s a lane’s distance but that’s not very far when it’s heat and flames going across.”
First Minister Nicola Sturgeon said the incident appears to be “extremely serious”.
Speaking at First Minister’s Questions, she said: “This is a deeply concerning incident in the city of Glasgow.”
She praised the firefighters tackling the “extremely challenging” blaze and said the Scottish Government’s resilience unit will remain in contact with the fire service throughout the incident.