A number of properties have been evacuated and around six fire engines are dealing with the incident on Sauchiehall Street near the junction with Hope Street.
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.”