The crash happened around 7:17 p.m. in the southbound lanes near the Route 141 off-ramp in Newport, Delaware.
Investigators say the driver of the truck, 42-year-old Brian Jubb, began to merge out of the center lane and, for an unknown reason, kept going into a grassy area off the highway.
Police said the 2004 Chevy Silverado then overturned several times down a steep embankment before coming to rest in a marshy area.
Jubb's passenger, 45-year-old Donna Jubb, was not properly restrained, police said, and was ejected from the truck. She was rushed to the hospital but was pronounced dead at 10:17 p.m.
Brian Jubb, who police said was properly restrained, suffered non-life-threatening injuries.
A dog riding in the truck was also killed, police said.
A single lane of southbound I-495 was closed as the crash was investigated and cleared.
Police say an investigation continues and that alcohol is not considered to be a factor in this crash.