The woman was driving southbound around 11:30 p.m. when the collision occurred just north of Barrie. Her vehicle reportedly swerved into a ditch, then back into traffic, slamming head-on with an oncoming vehicle.
The female motorist died at the scene. The driver of the northbound car suffered serious but non-life-threatening injuries. The passenger in the woman's vehicle was also rushed to hospital, but is also expected to survive.
The OPP was investigating the crash and the highway was closed for several hours but has since reopened.
The deceased's name has not been released.