It happened around 9:20 p.m. just north of Exit 7A in Robbinsville, Mercer County.
Police said the tractor-trailer hit a bridge abutment in the inner drive of the northbound lanes, spilling watermelons all over the roadway.
New Jersey State Police said the driver and a passenger were killed in the crash. There is no immediate word on their identities.
The crash briefly shut down the northbound lanes of the Turnpike near mile marker 60.3.
By early Friday morning, just the right shoulder was blocked in the inner drive to traffic. All lanes were reopened by 6:30 a.m.
Police are still investigating the cause of the crash.