Officers were called to the scene on the A614 near Middleton on the Wolds at 4.30pm on Sunday.
A grey Yamaha motorcycle and a yellow Peugeot car collided between Middleton on the Wolds and Market Weighton.
The driver of the Peugeot also suffered serious injuries.
A spokesperson for Humberside Police said: "Our thoughts are with the man’s family and friends as they come to terms with their loss. They are being supported by specialist officers at this difficult time."
Police are also appealing for witnesses who may have dashcam footage or saw the accident or the vehicles prior to the crash.