A 37-year-old man was declared dead at the scene and a 54-year-old woman was taken to hospital, where she was later pronounced dead.
Bob Lemle of Urgences Santé said they died as a result of smoke inhalations and severe burns.
A female relative of the two who died was treated for shock. Dozens of residents were forced to leave the building and were taken in by the Red Cross.
Around 50 firefighters were on the scene.
The fire started in an apartment on the third floor of three-storey building on Matte Street, near Maurice-Duplessis Boulevard.
The cause of the fire remains undetermined. As per protocol, the case has been transferred to the Montreal police as a criminal investigation because of the deaths.
This comes just under a year after another cooking fire in an apartment directly across the street claimed the life of a four-year-old girl.
In that incident, the home was not equipped with a functional smoke detector.
It is not known if the apartment involved in today's fire had a working smoke detector. Police said investigators would be looking into the question as part of the investigation.