Nabi Magomedov, 35, and Natalia Shcherbina, 32, and their 3-year-old son, Amir Magomedov, all of Rochester, were killed when a tractor-trailer crossed from the southbound lane and smashed into the family's sport utility vehicle in the northbound lanes.
The family, Russian citizens, was pronounced dead at the scene and later taken to Horton Medical Center in Middletown, state police said.
The truck's driver, 63-year-old, Andrew McKiver of Roosevelt, New York, was airlifted to Good Samaritan Hospital in Suffern, where he later died, said Sergeant L.D. King of state police Troop T in Newburgh.
Sergeant King said that all four people died from head and chest injuries.
The accident occurred at 1 p.m. about two miles south of the Harriman toll plaza, near Exit 16.
The truck hit with such force that the SUV was jammed into a car carrier traveling on the SUV's other side.
The driver of the car carrier was uninjured, but a Jaguar it was hauling was totaled.