The wreck occurred at mile marker 21, near Old Milburnie Road, shortly after 3 p.m., according to the state Department of Transportation.
Two cars, an Utz food-delivery truck and a pickup truck carrying furniture were involved in the initial wreck, officials said. A van and a Ryder truck got tangled up in the collision while trying to avoid the mess.
Officials said that at least three people were transported to a local hospital.
I-540 West was completely shut down for a while, but all lanes were reopened by 5:30 p.m.