It happened around 1 p.m. near Olive and Angus.
Firefighters say there was heavy smoke coming from the home, and a woman was trapped inside.
Crews rescued her, attempting CPR and other life-saving measures but she appeared to be unresponsive.
Investigators say her injuries are life-threatening and an investigation has been launched.
"This is now a crime scene when someone is injured at a house fire like this," said Rich Cabral. "Similar to developing a criminal type of case."
Firefighters say this investigation is expected to last for several hours. It's too early to tell the cause or the origin, but it appears the area with the heaviest smoke was around the living room.