The shooting was caught on camera and posted to Facebook, where it currently has more than 50,000 views.
Witnesses said the teen was unarmed.
Video footage, which was captured by Shauny Mary, shows a car stopped in a residential street.
The driver of the car is being handcuffed when two people flee from the car, one at a time, with their backs turned to the officers, seconds before three gunshots can be heard.
One of the men, identified as a 17-year-old boy, falls to the ground after shots are fired.
"Why are they shooting at him," Mary asks after the shots are fired.
"All they did was run and they’re shooting at them?"
The 17-year-old, who died at the hospital, has not yet been named.
One video shows paramedics attempting to revive the teen in an ambulance, but their efforts are unsuccessful (warning graphic).
It happened Tuesday evening in East Pittsburgh in Allegheny County, which is located about 15 minutes outside of Pittsburgh.
Police said the incident started with another shooting in the neighborhood, although video doesn't appear to show whether or not the teen is in possession of a gun as he flees from the car.
“At approximately 8:20 PM, County 9-1-1 received multiple calls reporting that shots were fired and that a male had been shot in the 800 block of Kirkpatrick Avenue,"North Braddock police said in a written statement.
"Callers reported that a vehicle was seen fleeing the scene, and were able to provide a description of that vehicle. North Braddock Police and paramedics responded and found a 22-year-old male who had been shot. He was been transported to a local trauma center where he was treated and released."
Allegheny County police also issued a written statement regarding the shooting.
Information on the vehicle that fled the North Braddock scene was put out over the air for neighboring police departments to assist/respond. An East Pittsburgh police officer saw a vehicle matching the description on Grandview Avenue which also had ballistics damage to the rear window. The officer stopped the vehicle near Grandview and Howard Street in East Pittsburgh. The officer took the driver into custody. While he was putting the driver into handcuffs, two other occupants ran from the car. One individual – a 17-year-old male – was shot by police. He was transported to McKeesport Hospital where he was declared deceased. Further information on the deceased, including name, will be released by the Allegheny County Office of the Medical Examiner once formal identification has been made and the next of kin notified.
The driver, who was not shot, was handcuffed and apparently arrested, although his name has not been released and it's not clear whether or not he'll face any charges.
Police say they are still searching for a third person who ran from the vehicle, according to Heavy.
Currently, the Allegheny County Homicide Unit is investigating both incidents.