It happened just before midnight on Washington Avenue and South 20th Street in the city's Point Breeze neighborhood.
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Officers say an unknown vehicle, possibly an Infiniti, was traveling eastbound on the 2000 block of Washington Avenue at that time.
A pedestrian was walking southbound across Washington Avenue when he was struck by the vehicle.
The impact caused the pedestrian to land on another unknown vehicle, which also may have been an Infiniti.
Both cars fled the scene after the incident, police say.
The victim was transported to Jefferson Hospital with severe head trauma. He is listed in extremely critical condition.
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There is no word yet on his age or identity.
Infiniti car parts were recovered from the highway after the collision, according to investigators. It is unknown if the parts came from either vehicle involved.
Police say they also found a shoe left behind at the scene.
Neighbors in the area say cars speed constantly along Washington Avenue, making the roadway dangerous.
"They fly through here. They think it's a raceway," said John Nicotera from Point Breeze.
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Because of this, people say while this collision is tragic, it is not unexpected.
"Not surprised, not surprised," said Nicotera. "Even if you have the light and you're crossing the street, you still have to worry about somebody blowing the light and hitting you. It's pretty bad along here."
He's worked in the area for 35 years and says problems are even worse since the city changed the traffic pattern by reducing driving lanes and adding the bicycle lane.
Action News spoke with one couple out on their nightly walk, who say they are much more cautious of Washington Avenue after hearing the news.
"When it's like that, hard red, I will not go until that walk sign turns on. Even when I look at the walk sign, I double look each way," said Kathleen Boltey from Point Breeze.
Other residents are just hoping that police catch the drivers involved.
"With everything going on in this city, I just wish everyone would look after one another. If something were to happen, just stop. And make sure the person is ok. Just more tragic than anything," said Tim Erb from Point Breeze.