The incident happened just before 2 p.m. Thursday on the 9000 block of East Roosevelt Boulevard.
"That's brutal," said William Keiper of Northeast Philadelphia. "That's one of the worst accidents I've seen."
Police said a man was driving in the outer lane when he struck two pedestrians.
The van ended up on its side in pieces next to a tree. Several Philadelphia firefighters worked with care to remove the driver from the vehicle.
"Our assets have to go into service with heavy rescue tools to essentially and strategically open this vehicle to not only increase any harm to the person that's inside the vehicle, but on top of that make sure we safely extricate him," said Philadelphia Fire Acting Executive Chief Daniel McCarty.
Police said the driver was later pronounced dead at the scene.
Both pedestrians were taken to the hospital, where one died and the other remains in critical condition.
"It's a shame. It's crazy how one minute everything is going on, and then the next minute, something unfortunate happens and then it's all over," said Ryan Collins of Northeast Philadelphia. "I feel bad for anyone who lost a family member."
"My thoughts and prayers are with them. This is a horrific accident," added Keiper.
The van belongs to Raymond Arbor Pengate in Willow Grove. The company provides material handling services, including forklifts and other equipment.
The victims have not been identified.
The cause of the crash remains under investigation.