Emergency crews responded to the fire, in an abandoned building behind the Food Basics grocery store at Lauzon Road and Tecumesh Road East, at about 6:20 p.m. Wednesday.
A dark cloud of smoke could be seen billowing across the city's sky from kilometres away.
Firefighters closed off the nearby intersection and urged a large crowds of people to stay back.
No chemicals inside, fire chief says
The longtime chrome plating plant was acquired by the City of Windsor for back taxes in 2009.
The City had trouble selling the building due to potential contaminants including chromium, copper and nickel that were left behind when the factory closed in 1990.
Lee Tome, the city's chief fire prevention officer, told reporters none of those were still present inside the building.
"Back in 2010 an environmental assessment was done, the City took ownership and cleaned up this property of all the chemicals that were in it," said Tome.
"We're confident that there is no chemical storage in the building."
He said the black smoke was caused by the asphalt roof burning, and not possible contaminants.
Battle will continue through the night
Tome said the fire had moved to the building's north side and expected fire crews to be there throughout the night.
"We have had some collapse to the southeast corner and to the front of the building. "Structurally we don't want firefighters in the building, there are some deep pits in there and we're not going to be putting anybody in that building."
Firefighters continued to hose the building down from the outside.
Rob Costello saw the black cloud of smoke while driving back from his daughter's soccer practice.
"We saw a lot of black smoke and a whole bunch of traffic and a lot of firefighters," said Costello.
Costello said he drove over from a distance concerned the fire could have been near his home.
"Number one concern is this back smoke, and what it's putting in the air, we live in the area and so we're a little bit concerned about that."