Four other male victims, including a teenager, were wounded.
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The victims are among the more than 30 people who have been shot this Labor Day weekend in the city.
The gunfire erupted just before 1 a.m. in the 700 block of W. Russell Street.
There were a large number of spent shell casings, which indicate a number of shots were fired.
Police are still working to figure out who opened fire, and why. No arrests have been made and no suspects have been identified.
"My heart is heavy right now, my chest hurts," said Sister Taleah Taylor, the president of City of Dreams Coalition, a nonprofit fighting violence in the city. "It's nothing new, it's all over the nation. When are people going to wake up?"
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One of six people shot in this incident, a 33-year-old woman, was pronounced dead at the scene. She suffered gunshot wounds to the head and shoulder.
A 19-year-old man with multiple gunshot wounds to the body was pronounced dead at the hospital shortly after 5:30 a.m.
The names of the victims who were killed have not been released pending family notification, police said.
Of those who were wounded, two of them - a 23-year-old male and a 55-year-old male - are in critical condition with multiple gunshot wounds.
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The other two, a 17-year-old male and a 31-year-old male, are in stable condition.
Officers established a second scene outside Temple University Hospital and placed crime scene tape around an SUV that had bullet holes in the side.
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In a tweet, Mayor Jim Kenney called the violence "devastating and unacceptable."
"The amount of violent incidents over this holiday weekend is devastating and unacceptable. Philadelphians deserve to be safe in their communities. My deepest sympathies go out to all those affected by this senseless violence, especially families that have lost loved ones," the tweet said.
In another shooting at 46th Street and Lancaster Avenue, a 19-year-old was killed near a drive thru in West Philadelphia on Sunday afternoon.
"It's normal," said Kiayh, a West Philadelphia resident who did not want to give her last name. She spoke to Action News just feet from the scene of that shooting. She was out walking with her son, and said the violence has been increasing.
"It's getting worse and worse," she said. "People like me we just try to stay indoors, work hard see if we can get out of here."
Since Saturday evening, 10 people have died in 22 difference shootings across the city.