The crash happened about noon on the southern side of the Hawke's Bay Expressway Meeanee overbridge.
The woman was driving towards Napier and approaching the overbridge when her car was seen to veer across the centre lane, swerving between two oncoming cars before crashing into a drainage ditch.
Police said no other vehicles were involved and there were no immediate indications as to what caused the car to veer off the expressway.
Two doctors and an advanced paramedic worked on the woman for about 20 minutes but she died at the scene.
A second fatal crash at an Otane intersection cost the life of a 35-year-old Central Hawke's Bay man who died at the scene.
Three passengers in a second vehicle are in stable condition at Hawke's Bay Hospital today.
Waipukurau Police Sergeant Denis Tatere said the dead man was the only occupant of a station wagon that hit the back of a north-bound hatchback about 6.45pm.
The victim's car had hit a power pole and rolled on to its roof.