The crash happened near the intersection of Peter and Richmond streets.
Witnesses who spoke to CBC News claim that the bus ran a red light while it was heading north on Peter Street, hit two vehicles, including a taxi, and then struck a building.
Thomas Rokih was shaken after the rental car he was driving was struck.
“We had a green light, I wanted to go through and the bus came from the left,” Rokih told CBC News.
“I tried to brake ... we nearly came to a stop, but we hit the bus on the side and the bus went into the cab there and then into the wall.”
The bus driver and two passengers were taken to hospital with non-life threatening injuries, as was the taxi driver.
Toronto police will review video from nearby cameras to determine if the bus driver did in fact run a red light.
Peter Street remained closed between Queen and Adelaide streets for several hours, as police investigated the crash.