Witnesses told local media the OC Transpo Route 269 bus swerved moments before slamming into the bus shelter overhang at the Westboro station west of downtown.
Several people found themselves trapped on the bus' upper level following the crash, and most serious injuries happened on the vehicle's upper right side, said Ottawa Police Chief Charles Bordeleau.
There were three people killed in total - two on the bus, one on the platform. The Ottawa Hospital confirmed on Twitter that it had received nine patients in critical condition from the crash.
The driver was detained at the scene and he was set to be interviewed by police.
His partner usually gets off the bus at that station when coming home from work but she hadn't gone in on Friday, he said, and now they're checking in with all their family and friends who live in the area to see if they're OK.
"Like Ontarians from across the province, I was shocked and saddened to hear of the awful tragedy at Westboro station in Ottawa".
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The investigation will take a long time and likely will mean the closure of the busway and nearby roads for at least many hours, Bordeleau said. He saw first responders cutting out seats and windows from the top floor of the bus and described the front of the bus as being "essentially cut off" or "demolished".
Ottawa Mayor Jim Watson tweeted he was shocked to hear of the "horrific incident".
John Manconi, the general manger of OC Transpo, which runs Ottawa's public transit system, said that at least 90 people could have been on the bus.
Emergency crews respond to a deadly double-decker bus crash at Westboro Station in Ottawa, January 11, 2019.
In 2013, another Ottawa double-decker bus broke through a warning gate and collided with a Via Rail train in suburban Barrhaven, killing six people as the train sheared off the front of the vehicle.