Investigators determined the blaze was sparked by an e-bike battery charging inside the home.
The fire broke out around 4:45 a.m. Friday in the 2600 block of S. Mildred Street.
"Looks like a heavy bulk of fire started on the first floor. You'll see the whole front is burnt out. Inside, a lot of fire there this morning," said Philadelphia Fire Department Executive Chief Daniel McCarty.
Neighbors described a chaotic and devastating scene, with some waking up to screams for help as the fire tore through the residence.
Women dead, child among 2 others hurt in South Philadelphia house fire
Surveillance video captured a series of blasts coming from the home, followed by a man seen outside in a panic. Minutes later, firefighters arrived on the smoke-filled block.
"All first responders were here. It was chaotic," said Chris Adams of South Philadelphia.
Firefighters located two victims inside the home, according to McCarty.
"Two were found in the first-floor kitchen area. It looks like they potentially awoke to the smoke and fire. I can't confirm that I was not there, but preliminary, where they were found by our responders, it looks like they were trying to make it out," McCarty said.
One woman, identified as a 49-year-old, later died from her injuries, while another was hospitalized and listed in stable condition.
A child rescued from the home - identified by family members as a 4-year-old girl - was taken to Children's Hospital of Philadelphia in serious condition and is now reported to be in critical condition.
Adams said he rushed outside after hearing screams.
"We have a skylight. And I could hear somebody screaming, extremely loud. I've never heard -- it was like bloody violence," he recalled. "It was crazy."
Officials say they were able to contain the fire within 15 minutes of arriving on the scene.
Family members rushed to the block as the situation unfolded, searching for loved ones.
"We drove here really quickly. My fiancé is at the house checking everything out. And I'm just trying to find her, that's the gist of everything that I know," said Joe Kobielnik of Vineland, New Jersey.
The building's owner said the tenants had lived there since January and described them as close to him.
"They're a good friend of mine. They're like my family. I'm sorry for your loss," said Ronnie Mirchandani. "The 4-year-old daughter is in critical condition. I hope she gets well and she's OK. I'm not worried about the house."
Photos taken at the scene showed a charred e-bike outside the residence.
Despite the cause, neighbors said the loss has shaken the community.
"I'm heartbroken. Anytime someone loses a life, it's significantly tragic," said George Pond of South Philadelphia.
Officials initially reported they could not hear smoke alarms when firefighters arrived. A subsequent investigation determined that there were working smoke alarms inside the home, but they had melted due to the intensity of the fire.
The victims' names have not been released.