It happened just after 9:30 p.m. on the 3100 block of North Croskey Street, near Clearfield Street.
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Video obtained by Action News showed smoke billowing from the home as crews worked to contain the blaze.
Officials said three of the residents inside jumped from the second-floor window of the house to escape the fire.
"I witnessed one of them jump out of the second floor window to the ground," said Tyron Martin, who witnessed the fire and recorded video of the intense flames.
He heard commotion outisde of his nearby home and then saw the flames. He said the people inside were desperate to escape.
"They were trapped. They couldn't get out, it was just ad to hear the screams and hollers," Martin said.
Authorities say four victims were located in two different parts of the property.
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A 58-year-old woman and a 62-year-old man were pronounced dead at the scene.
A 39-year-old man who jumped was taken to Temple University Hospital where he was pronounced dead just before 1 a.m. Tuesday.
A 34-year-old man was taken to Temple Hospital where he is listed in critical condition.
A demolition team was brought in on Tuesday to tear the building down because of safety concerns.
Family and friends of those who died stood and watched as the building was slowly torn down.
"I'm going to miss her," said Kenneth Hicks, a friend of the woman who died. "She was a wonderful ladya nd she always looked out for everybody."
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Another man, who identified himself as the son-in-law of the couple killed in fire thanked people for their help.
"I just want to thank everybdoy for what they could do, and what they did do. Keep us in Y'alls prayers," he said.
The fire is under investigation.
The assistant fire chief urged people to make sure they have working smoke detectors.