Firefighters were called to the home on the corner of Beacon Hill Road and Southgate Street just before 10 a.m.
They found flames in the basement, and managed to contain most of the damage to that part of the house.
Three people were taken to hospital and one did not survive.
Another person was treated at the scene.
Firefighters say they believe the man who died was in the basement at the time of the fire.
A worker who was repairing a nearby water main told CBC that the residents were an elderly couple, and that it was their adult son who died.
Montreal's arson squad is now taking over the investigation, and say at this point there's no information available on the likely cause of the fire.
Investigators do say that the house was equipped with smoke detectors.