Four people escaped from the terraced home on Field Road, Forest Gate, before firefighters arrived shortly after 04:42 GMT.
Crews found the man's body on the ground-floor of the two-storey house.
Police are treating the death as "suspicious" and officers believe "the fire was started deliberately".
Twenty one firefighters and four engines tackled the blaze, which was brought under control after about two-and-a-half hours.
The man, believed to be in his 60s, was pronounced dead at the scene.
Officers are awaiting formal identification.
Det Ch Insp Steve McCabe said: "I need to hear from anyone who saw anything suspicious in Field Road and the surrounding area in the early hours of Christmas Day."
A murder investigation has begun after the body of a man was found after a house fire in the early hours of Christmas Day.