Firefighters and police were called to the blaze at Toll Bar Houses, in Distington, at 4.47am
A 58-year-old man and a 14-year-old girl, both from the village, died at the scene, police confirmed.
Neighbouring properties were evacuated and there were no other reported casualties. The cause of the blaze is being investigated by Cumbria Police and the fire and rescue service.
Motorists are being urged to avoid the area.
A number of roads remain closed as emergency services deal with the blaze including the A595, which is closed southbound between the roundabout near Dobies’ dealership and the roundabout at Howgate.
The A597 is closed between the roundabout near the Toyota dealership and the junction of Hallywood Road.