The blaze broke out in Queens Road in Somersham, Cambridgeshire, at about 20:00 BST on Monday.
The two people died at the scene, police said. Neighbouring houses were evacuated as the firefighters spent about three hours tackling the blaze.
Police said they were not treating the fire as suspicious. The cause is not yet known and the fire service is continuing its investigation.
More on this and other news from Cambridgeshire
A man and a woman have died in a house fire.