It happened around 9:45 p.m. on the 3600 block of Germantown Avenue near Max's Steaks in the city's Tioga-Nicetown section.
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Police tell Action News that the shooting critically injured a 34-year-old man and an unidentified male victim.
Two others, an 18-year-old woman and a 33-year-old man, are listed in stable condition after being shot, said police.
SEE ALSO: 16-year-old arrested in shooting of 7 people outside Golf and Social Club in Fishtown
Chopper 6 was overhead as officers cordoned off an area near the busy intersection of Erie and Germantown avenues.
It's still unclear what led up to the gunfire.
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No arrests have been made.
Anyone with any information is asked to call police at 215-686-TIPS.