Stanhope CFA captain Chris Dent said his brigade received the callout about 2.30am to a property on Girgarre East Rd.
He said the fire had engulfed most of the house by the time firefighters attended the property, and there was "nothing crews could do" except stop it spreading.
More than 40 volunteer firefighters and 13 vehicles responded to the blaze, from as far away as Echuca.
The two residents of the single-storey home escaped uninjured after being alerted to the blaze by smoke alarms.
“Thank god for smoke alarms,” Mr Dent said.
“Unfortunately the house was a total loss.
“I couldn't feel sorry enough for them, but at least they have their lives."
A CFA spokesperson said the fire was brought under control by 3.35am and the final crews left the scene about 8am.
An investigation into the cause of the blaze is under way but at this stage it isn't being treated as suspicious.
Ambulance Victoria and Victoria Police also attended the incident.
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