Emergency crews were called to the crash on Wellington Road 124 near Sixth Line at around 5:30 p.m.
OPP said a silver sedan and a school bus collided head-on, and a young man was rushed to a trauma centre with life-threatening injuries.
A teenager in the car was also taken to hospital, but her injuries are considered non-life-threatening.
The woman driving the school bus was treated for minor injuries at the scene.
Police said no one else was on the bus at the time of the crash.
Neither the identities of those involved nor their ages were provided by OPP.
Wellington Road 124 was closed for several hours but has since reopened.
The cause of the collision is still underway, and police said it’s too early to comment on any possible charges in the investigation.
Wellington County OPP is asking any witnesses to contact them at 1-888-310-1122.
WATCH: Speeding pickup truck slams into a home, leaving a gaping hole in the basement wall