According to authorities, the crash happened just before 10:30 p.m. in the southbound lanes of I-495, between the Edgemoor and Philadelphia Pike exits.
Four vehicles were involved in the crash and several other vehicles were struck by debris.
One person was killed and at least one other person was injured, authorities said.
The road is expected to be shut down for several hours.
There was no information provided as to what caused the crash.