The crash happened at 3:35 p.m. on the northbound side between Route 896 and a highway rest area.
Delaware State Police say the crash involved a tractor trailer, a minivan and two SUV's.
Images from Chopper 6 HD over the scene showed a large crash scene.
The tractor trailer ended up in the middle of some trees after it skidded off the highway.
It was not immediately clear how many people were injured. All the injuries were said to be non-life-threatening.
All lanes of I-95 northbound were closed for more than an hour as crews worked to clear debris.
Traffic was backed up for miles.