York Regional Police say the crash occurred at 6:15 p.m. Wednesday, when a northbound Chevrolet Cruze crossed the centre line of Woodbine Avenue, south of Holborn Road, and struck an oncoming Acura CSX.
Police say the 46-year-old driver of the Acura was taken to hospital, where he later succumbed to his injuries.
The Chevrolet driver suffered life-threatening injuries in the crash. He is 72 years old.
The crash remains under investigation.
Anyone with information is asked to contact police at 1-866-876-5423, ext. 7704. Information can also be passed on anonymously through Crime Stoppers at 1-800-222-8477.