It happened around 7:30 a.m. at exit 287 for Harrison Avenue.
Details surrounding the accident have not been released, but one person may have been hurt in the crash. Eyewitness photos at the scene showed the 18-wheeler flipped over on its side behind another big rig.
The two right eastbound lanes of I-40 are closed while officials work to clear the scene.
The lanes are expected to re-open by 10 a.m.
Driver are being asked to avoid the area if possible.
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