Five fire crews were called in to help after reports of smoke and flooding at the property in Framfield Road, Uckfield.
Part of Uckfield High Street remains closed this morning following the house fire, with two fire crews still on scene.
A spokesperson for East Sussex Fire and Rescue Service said no one had been hurt.
She said: “Firefighters from Bexhill, Uckfield, Lewes, Crowborough and Brighton all attended and on arrival there was smoke issuing from the roof.
“All persons self evacuated.
“Crews used six breathing apparatus, foam, one jet hydrant and an aerial ladder platform.
“Investigators are going there today or tomorrow to investigate the fire. The cause is unknown.”
The road closure is Framfield Road, listed as High Street (B2102) both ways between Alexandra Road and High Street, near Buxted station.