Fire crews, cops and paramedics descended on the home, where a woman in her 30s was found dead.
Cops are now probing the lethal blaze – after five engines from four stations in the region battled to put it out.
Greater Manchester Police said: “At 4.22am on Sunday we were called to reports of a fire at a house on Roundthorn Road, Middleton.
“Emergency services attended, and sadly a woman in her 30s was found inside the house deceased.”
The force added: “An investigation is underway to establish the circumstances.”
Fire & Rescue Area Manager Lee Coleman said: “At around 4.20am yesterday morning, five fire engines from Middleton, Chadderton, Blackley, Phillips Park and Manchester Central fire stations attended a house fire on Roundthorn Road, Middleton.
“Crews wearing breathing apparatus arrived quickly and used four hose reel jets and one nine-metre ladder to extinguish the fire.
“Firefighters remain at the scene.”
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