The crash happened around 1:42 p.m. in the 4000 block of Route 34 near Wolf Road in Oswego, police said.
A 20-year-old man riding a motorcycle eastbound on Route 34 when it crashes into a trailer being towed by a van as it was attempting to turn right into a driveway, police said.
The motorcyclist was taken to a hospital, where he was later pronounced dead. His identity has not yet been released. An autopsy is scheduled for Monday.
Route 34 was closed between Wolf Road and Boulder Hill Pass for about four hours as police investigated the crash.
No other injuries were reported in the crash.