Several other people were injured, the Montreal Gazette reported.
The impact of the crash was so violent it apparently forced the bus driver partly out of a window, police said. He died when the bus turned on its side.
A 61-year-old passenger in a BMW was thrown from the car, becoming the second fatality. The driver of the BMW was hospitalized with critical injuries in the chest and head, police said.
Police used planks in an effort to lift the bus off the driver's body. His identity was not released, but police said he was 50 and worked for STM, the Montreal transit agency.