The crash happened on the B1348 at Seton Dean, close to Seton Sands Holiday Village, around 2.20pm on Saturday.
Emergency services attended and the man was taken to Edinburgh Royal Infirmary, however he died en route.
Police are appealing for more information.
A police spokesman said: "Police in East Lothian are appealing for witnesses after a fatal road collision in Longniddry.
"The incident happened around 2.20pm on Sat 20 April, on the B1348 at Seton Dean east of the Seton Sands Holiday Village.
"A 21-year-old motorcycle rider sustained serious injuries when his bike was involved in a collision with a Volkswagen Golf.
"He was transferred to the Royal Infirmary of Edinburgh but sadly died en route.
"Inquiries into this collision are ongoing and anyone with any information is asked to come forward."