Officers responded around 2:30 p.m. on Sunday to the area of Guelph Line near Campbellville Road and the south entrance to the casino.
Investigators said the collision was between a car and a motorcycle. Two people on the motorcycle were injured.
Police said a 55-year-old woman sustained minor injuries, while a 67-year-old man was seriously injured and both have been taken to Hamilton General Hospital.
Officers said the Collision Reconstruction Unit has been called as well as the Forensic Identification Bureau.
The investigation remains ongoing.