The crash happened around 2:00 a.m. in the southbound lanes of the New Jersey Turnpike in Mount Holly, Burlington County, just north of Exit 5.
The inital investigation showed that the 2007 Freightliner box truck was traveling south in the right lane when the driver lost control, slammed the right guard rail, and flipped on its right side.
The truck kept moving forward, struck the support column of an overpass and flipped back on its left side, before bursting into flames.
Police say the truck was fully engulfed when emergency crews arrived.
The driver, identified as 67-year-old Joseph Gaudio of North Carolina, was able to safely exit the truck. He told a New Jersey State Trooper that his wife was still inside, in the passenger compartment of the truck.
67-year-old Glenda Gaudio was later pronounced dead at the scene.
Joseph Gaudio was taken to Mount Holly Hospital for treatment of minor injuries.
Police continue to investigate. They would not say if thick fog in the area contributed to the crash.
Engineers were checking the overpass hit by the truck for structural damage.
Commuters were advised to expect lane closures throughout the morning. Oxmead Road was closed between Bromley and Burrs Roads as crews worked to clear the scene.