Crews first heard about the four-alarm fire at the abandoned house at 301a George Street at about 4:20 a.m. Thursday.
Firefighters say they brought the blaze under control at about 8:20 a.m., with only the odd puff of white smoke coming from the roof. The fire gutted the building.
The rear of the building was fully ablaze when crews arrived. Flames and thick plumes of smoke could be seen coming from the building. Firefighters battled the blaze for more than three hours with cranes because they couldn't move to the building's weakened upper floors.
The house was ablaze from the second floor joists up through the third floor and into the roof, the fire department said in a news release.
Residents in the neighbourhood said people often squat in the building, which isn't the only vacant property on the street.
There have been a couple of other fires in those vacant homes of late, said neighbours.
"I'd say within the last two months they've had a couple of bad smoke [incidents] in those abandoned ones. The fire department's been here twice for those," said resident Judy Gardner.
"It's bad. The city has to do something about it."
Local councillor Kristyn Wong-Tam, who was on the scene, said the city is pressuring — and will continue to pressure — the owners of the vacant buildings to fix them up so people can live legally in them.
"The buildings have been an issue for the community for some time," Wong-Tam told CBC News in an interview on Thursday.
Wong-Tam said both she and the community are losing patience with the ongoing problems, which include security issues and a "proliferation of illegal activity taking place."
There were no reported injuries as there were no people in the building. The neighbouring apartment, which is occupied, was safely evacuated, and firefighters rescued two cats.
The fire department said anyone in the area who smells smoke from the blaze should keep their windows closed.
The Ontario Fire Marshal has been notified.