The crashes all happened near NC-86 around 5:30 p.m.
For nearly five hours, the westbound lanes of the highway were closed. Two of the eastbound lanes were also blocked.
Durham police said three vehicles, including the tractor-trailer, caught fire but no one suffered major injuries.
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Several people were taken to the hospital for treatment, but none of the injuries appeared to be life-threatening, according to the Durham Police Department.
I-40 West reopened about 9:30 p.m.