The crash happened around 5 p.m. Friday in Radnor, Delaware County.
Police say it all began when the driver of a tractor-trailer did not stop in time to avoid slow traffic in the southbound lanes.
The driver swerved to avoid a collision, but hit another tractor trailer.
The impact sent both big rigs into the northbound lanes where one of those trucks hit a third tractor trailer.
The driver of the truck who failed to stop was killed. One other injury was reported.
All lanes of Interstate 476 reopened around 4:30 a.m. Saturday.