Four fire engines and around 25 firefighters were called to a fire at a house on Hambalt Road in Clapham.
Most of the ground and first floors of the three-storey building were damaged by the fire. The internal staircase and a small part of the second floor were also damaged.
Firefighters wearing breathing apparatus rescued one man from the ground floor using a fire escape hood. He was taken to hospital by London Ambulance Service crews, where he sadly later died. Another two men were treated at the scene.
Sub Officer Carl Isaacs, who was at the scene, said: "Firefighters worked incredibly hard to quite quickly get the fire under control, which aided the rescue of the man by breathing apparatus crews.
"He was on the ground floor of the property and firefighters bought him out using a fire escape hood.
"Fire escape hoods provide members of the public with up to 15 minutes protection from four of the main fire gases (carbon monoxide, hydrogen cyanide, hydrogen chloride and acrolein) and can be worn by conscious or unconscious people.
"If more than 15 minutes protection is required then another hood can be given to each wearer. They do not provide oxygen but temporarily filter toxic smoke to make breathing easier."
The Brigade's 999 Control Officers took 10 calls to the blaze.
The Brigade was called at 0100 and the fire was under control by 0237. Fire crews from Clapham, Battersea, Brixton and Tooting fire stations were at the scene.
The cause of the fire is under investigation.