Emergency services were notified of the fire at the Roots department store on Queen near Peter Street at just around 1 a.m.
When fire crews arrived, they found flames shooting out of an upper floor. High winds created more problems for firefighters as they struggled to extinguish the blaze, and there were fears the building would collapse.
No one was inside the building when the fire broke out, and no one is believed to be hurt.
The Ontario Fire Marshall is investigating. Queen Street West is closed to traffic and pedestrians near Peter Street as firefighters put out the last hot spots.
Crews hope to have the street re-opened by the morning rush hour.