The fire started just before 3 a.m. at the single-family home on Vista Del Mar Avenue, according to the Los Angeles Fire Department. Firefighters quickly knocked down enough of the flames to search inside the home.
They pulled two people from the home.
The first victim, who was initially identified by the fire department as a teen girl but was later confirmed to be an elderly woman - died at the scene.
The second victim, identified only as a 70-year-old woman, was sent to a local hospital in grave condition.
Family members who arrived at the scene told Eyewitness News the victims are sisters who have lived in the home since immigrating to the United States in the 1970s.
"This is their family home since they came to the United States from Mexico," said Gaby Ruiz. "We don't know which is the one that passed and the other one, who is probably on her last moments."
A man who said he's the brother of the victims, speaking in Spanish, said that he previously lived in the home with them.
Early indications suggest the women may not have received a warning from smoke detectors.
"There is no immediate evidence of a functional smoke alarm," said LAFD Capt. Erik Scott. "So it's so important to remind everybody at home to ensure that you do have a functional smoke alarm. That gives you the early detection to get out and to stay out."
Investigators are working to determine what sparked the deadly fire and whether it could be linked to a recent series of rubbish fires reported in the neighborhood.
"There has been a spree of rubbish fires in the nearby area, as many as potentially eight last night and throughout the days prior," Scott said. "So that is knowledge that's been provided to the arson investigators, to law enforcement as part of the active investigation to determine if there's any sort of connection."
The cause of the fire remains under investigation.