The incident occurred at 4.30pm at the village of Bundtels in the northern part of the canton, southwest of Bern, the Swiss capital, cantonal police said.
The collision occurred at an intersection.
According to the initial evidence, it appears the woman driver did not see the bus and drove into the vehicle, carrying 30 passengers, the ATS news agency reported.
The force of the collision pushed the bus into a ditch to the side of the road.
The woman driving the car had to be extricated from the dented wreck by fire fighters, local daily La Liberté reported on its website.
She was transported to hospital along with a 60-year-old passenger in the bus who was also seriously injured.
Four other bus passengers suffered minor injuries.
Six ambulances responded to the accident.
Officials closed the highway temporarily between Guin and Böslingen and put a detour in place.