It happened just after 7 p.m. at the Staples location near Keele Street and St. Clair Avenue West in the city's west end.
Witnesses say a woman in her 50s was walking along West Toronto Street just west of Keele when she was struck by a piece of the large illuminated sign that stands above the parking lot.
At the time, the city was being battered by 100 km/h winds and heavy rain as the remnants of Hurricane Sandy was moving across the city.
Police tried to revive the woman after moving her to a safe location, but she was pronounced dead at the scene.
Police are now asking for the public's help in investigating what they are calling a "sudden death investigation."
"Early reports indicate that a portion of a large commercial sign had blown loose from its frame and fell," reads the police release.
A spokesperson for the company has told CBC News they are aware of the woman's death and are investigating the incident.
Police said the woman’s name would not be released.