The collision happened on Saturday around 7:30 p.m. ET, near the westbound exit 68 toward St-Alphonse-de-Granby, in the Eastern Townships.
For a reason that so far remains unknown, the driver of the semi-trailer truck plowed into at least one car while nearing a road work area at the bottom of a slope.
Two women who were riding in the same car were critically injured and later died in hospital.
Some of the others who were injured were trapped in their cars for hours before emergency responders could extract them and bring them to safety.
Sûreté du Québec spokeswoman Sgt. Mélanie Dumaresq said there was no criminal element to the investigation.
She said investigators will ensure the semi undergoes a full inspection to see whether it was in good working condition. The SQ will also look at whether the road work construction area played a role in the incident, and whether the truck driver was distracted or blinded by the sun.
The semi-trailer truck driver was not injured.
Highway 10 at St-Alphonse-de-Granby toward Montreal was closed until 5 a.m. Sunday.