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Earlier, the Highway Patrol confirmed two people died at the scene. Six people were initially reported injured in the crashes.
It wasn't immediately clear whether one of those people later died from their injuries.
Names of the victims have not been released pending notification of next of kin.
Sgt. Mike Baker told ABC11 that troopers were investigating one crash on I-40 near NC 210 when a second crash happened.
The second crash caused the most damage, he said.
A total of nine vehicles were involved between the two crashes -- including a tractor-trailer and a flatbed utility truck hauling lumber.
The driver of the truck carrying lumber failed to reduce speed for stopped traffic, Baker said, striking several vehicles causing a chain-reaction of multiple vehicle crashes.
Ten ambulances responded to the scene.
Most of the injured patients were taken to WakeMed for treatment.
All lanes of I-40 reopened by 7:30 p.m.
Delores Riewestahl of Angier was one of the many motorists caught in the congestion.
She was about three miles from the exit when traffic stopped.
"I was just praying for the families that were involved and just happy I wasn't involved because it could've been me if I had been a little bit farther down the road," Riewestahl said
Jo Williams was coming from Wilmington to Raleigh.
"Apparently, the accident had just happened because the firetrucks were merging off all the exit ramps coming in and when I got up there, there was a car that looked like it had almost been split in half, and it was on fire and the black smoke was huge. It was billowing up," Williams said.
She added: "I'm surprised there weren't more from the looks of that accident. That's sad."