Police confirmed the death, saying “a female stunt driver has died on the set of Deadpool during a stunt on a motorcycle”.
Local media has reported that the stuntwoman appeared to lose control of the vehicle, which drove off the set and through the window of a building across the road.
Images show police taping off a black Ducati motorcycle on its side next to a smashed office tower window in downtown Vancouver.
Witness Sharmina Kermalli said she had just walked into a Starbucks next door when she heard a loud crash.
She ran out of the coffee shop and saw glass still falling on the body of the woman, she said.
Dan Berger, spokesman for 20th Century Fox, said: “We are deeply saddened by the accident that occurred on the set of Deadpool 2 this morning.
“Our hearts and prayers are with the family, friends and colleagues of our crew member during this difficult time.”
Police said officers were at the scene and investigators with WorkSafeBC, the provincial workplace safety agency, were also looking into the crash.
Police have not yet released the name of the woman or details of the accident.
Another stuntman was killed in July during filming for The Walking Dead after falling onto concrete from around 25ft.
Deadpool, a Marvel Comics superhero, is played by Vancouver-born actor Ryan Reynolds.