Police said three bikers were headed south on Fayetteville Road when a car driven by Hazeline Rempson, of Durham, pulled out from Hanson Road and hit one of them.
It happened just before noon.
The injured cyclist, 33-year-old Tomas Sebastian Castillo, of Durham, was taken to Duke University Hospital, where he was pronounced dead.
Rempson and the two other motorcyclists were not injured.
No charges have been filed so far. The accident remains under investigation.