The pileup, which included a number of semis, happened Thursday night in the westbound lanes of Highway 16, about 45 kilometres west of Evansburg.
RCMP say there was also a two-vehicle collision in the eastbound lanes, which was also caused by reduced visibility.
The highway was closed for several hours to clean up debris, while people involved in the crash were taken to a reception area in Edson.
Another collision Thursday night southeast of Edmonton killed one person and left two others in hospital when a vehicle crossed the centre line on Highway 13 near Daysland and slammed head-on into a minivan.
The male driver of the van was pronounced dead at hospital.