The crash happened shortly after 4:30 a.m. at the intersection of Susquehanna and Fitzwatertown Roads in Upper Dublin.
Officials said an ambulance transporting a patient to Abington Hospital collided with another car, causing extensive damage that required emergency crews to cut one person out of the wreckage.
Surveillance video captured grainy images of the impact. Residents who live near the intersection said the sound of the crash was loud enough to wake them.
"I heard this really loud bang, a screeching noise, and I looked at the clock and it was 4:30," said Patrick Gallagher of Upper Dublin.
The ambulance, operated by the Second Alarmers Rescue Squad based in Willow Grove, ended up toppled onto a nearby property owned by a man who identified himself as Mike.
He said crashes at the intersection are not uncommon.
"A couple of years ago, somebody took the telephone pole out, came up on this section of the driveway. My wife's car was parked, totaled it," Mike said.
Officials said none of the ambulance crew members was injured. The two people hospitalized include the patient already inside the ambulance and the driver of the other vehicle.
Emergency crews used the "jaws of life" to remove the roof of the car and rescue the driver.
Both victims were listed in stable condition, though it was not immediately clear whether the patient suffered additional injuries in the crash.
Neighbors said drivers should use caution when approaching the intersection, especially given visibility and speed concerns.
"I have never personally had any issues during the day at least, but coming down the hill, you can get pretty fast if you're not paying attention," said Kyle Tompkins of Upper Darby.
Mike said the persistent safety concerns have weighed on him.
"If I would've known, I wouldn't have bought this house," he said.
Investigators have not said who may be at fault. The cause of the crash remains under investigation.