The one-car crash happened at exit 42 in Jericho, near the crossover to the Northern State Parkway just after 3:30 a.m.
It appeared the car bounced off the center divider before careening back across the roadway and coming to a stop on the right shoulder.
The 47-year-old man driving the Nissan SUV was rushed to the hospital, where he was pronounced dead.
Traffic was being diverted to the service road at the Jericho Turnpike exit at Route 106/107. The highway reopened just after 7 a.m.