Officials said the fire broke out at about 6:30 p.m. in the 2000 block of Bonnaffon Street. Heavy smoke could be seen from the first and second floors when officials arrived.
Police said the woman, who was in her 40s, along with a 4-year-old boy and a 1-year-old boy were found inside the home.
The woman was pronounced dead at the scene and the two boys were taken to CHOP, where they were later pronounced dead, police said.
Sirweah Quioh, who lives nearby, said when he saw the house burning, he rushed to knock down the front door.
"Only response she gave me was, 'I'm coming out, I'm gonna get the kids. I'm coming out', and that was the only thing she said," Quioh said. "Nobody came out."
After trying the back door, he stood helplessly outside the burning home and watched along with neighbors.
"By the time I hit the door to knock the door down, the smoke had already been all through the house. I couldn't get in the door any further. I just had to wait outside," he said.
Investigators have not released the names of the victims, but neighbors told Action News the children's father was at the corner store when the flames ignited and returned to the horrific scene.
The fire is under investigation.