The two-car accident happened on I-440 eastbound between Six Forks and Wake Forest Roads just before 4 a.m.
Police said one of the cars was traveling the wrong way.
Raleigh police said 25-year-old David Viva Xicotencatl was driving west on I-440 while 20-year-old Elizabeth Camille Bullock was driving east.
Bullock was declared dead at the scene. Xicotencatl died after being taken to WakeMed.
No other people were involved in the crash.
The accident shut down a section of I-440, but reopened around 8 a.m.