ISP said troopers responded to the crash on Interstate 290 eastbound at Interstate 294, near Berkeley, just before 1 a.m.
The crash involved a motorcycle and a black Honda, ISP said.
The motorcyclist was transported to a local hospital, where they were pronounced dead. Their identity was not immediately released.
All lanes were shut down, and traffic was diverted to southbound I-294 until about 6:30 a.m.
ISP is investigating. Authorities did not immediately provide further information.