Emergency services sealed off the scene at Howgate Street and nearby Galloway Street was also closed.
Local residents were urged to remain indoors and keep their windows closed. There were no reports of any injuries as a result of the incident.
A spokesman for the Scottish Fire and Rescue Service said the alarm had been raised at about 03:45 on Monday.
He added: "Crews were faced with a well-developed fire on arrival and they used high pressure hose reels, main jets and a water tower to tackle the blaze in the one storey commercial premises.
"The fire had also spread to an adjacent building.
"Firefighters also had to cool acetylene cylinders which were at the premises and they are continuing damping down operations at this time."
Police said that due to the scale of the fire a joint investigation into the cause would be carried out in due course.
More than 30 firefighters have tackled a blaze in a commercial garage in the centre of Dumfries.