The accident happened on the eastbound lanes of Wade Avenue around 1:15 p.m. Sunday.
According to a police report, 34-year-old Ray Rouse IV was traveling down Wade Avenue the wrong way when his car collided with a gold Mercury with two people inside.
Police said 83-year-old Ormond Bailey and 79-year-old Gaynell Bailey were in the Mercury and were both killed in the crash.
Rouse was taken to WakeMed with serious injuries. He is charged with DWI and traveling the wrong way on a dual lane highway.
According to court records, Rouse was convicted of DWI in September 2001 and sentenced to probation. He was again charged with DWI in 2006, but the case was dismissed.
Residents who live near the crash scene told ABC11 Sunday this is the second accident at the location in the past month.
"I have seen people drive the wrong way down this road several times, maybe it is confusing for some people," Tracy Strickland said. "Just a few weeks ago there was another accident, a slight head-on collision, and one of the cars actually ended up in our yard."