All three family members inside the car — a 47-year-old man, 42-year-old woman and their 15-year-old son — died in the crash.
A 79-year-old woman who was a passenger in the motorhome was also killed.
Her husband was airlifted by STARS air ambulance to an Edmonton hospital, where he is listed in serious condition.
RCMP say all five people involved in the crash are from out of the country, but have not yet commented on their nationalities. Their families are now being notified.
The crash happened about 25 kilometres south of Jasper. The highway was shut down for nine hours while emergency crews worked and an RCMP traffic analyst examined the scene.
The highway has now reopened.