The crash happened just after 12:15 p.m. on Highway 173 near Beauceville, 90 kilometres south of Quebec City.
The 62-year-old female driver was heading south when her car crossed the centre line and collided with a northbound car. She was pronounced dead at the scene.
Her 56-year-old passenger was taken to hospital in critical condition.
The other driver, a man in his 70s, is also in hospital with serious injuries.
The highway was closed until mid-afternoon, as police investigated the crash.