Around 3:45 p.m. on Monday, police said an SUV and a pickup truck collided head on.
The driver of the SUV was killed instantly, while the driver of the pickup truck was airlifted to Royal Columbian Hospital in New Westminster with non-life threatening injuries.
RCMP said the highway is closed in both directions.
Commuters are being advised to use Dewdney Trunk Road as an alternate route.
It is the third serious accident along this stretch of highway in recent days.
On Sunday, a crash sent two people to hospital with serious injuries and closed part of the Lougheed Highway in Maple Ridge for hours.
And last week, one person died and several more were injured when a Dodge Caravan crossed the centre line as it was heading westbound on Lougheed Highway approaching the Pitt River Road intersection.