Twenty fire engines and around 120 firefighters tackled a fire on the roof of a block of flats on Creek Road in Deptford.
The roof of the building was destroyed by the blaze and the external fascia was damaged. Around 13 people left the building before the Brigade arrived. There were no reports of any injuries.
Group Commander Richard Tapp, who was at the scene, said: "This was an intense fire located in the roof of the building and fire crews worked hard in challenging conditions.
"The fire was behind a number of voids which meant access was difficult and led to this being a protracted incident.
"It was a complex fire to fight and the roof of the building was destroyed.
"Crews initially worked to ensure there were no people inside the building and carried out a systematic search of all flats.
"We had two of our 32m ladders and a 64m ladder on scene which were key to stopping the spread of the fire.
"Firefighters remained at the scene throughout the night damping down any hot spots and were there throughout the following day (Wednesday)."
The Brigade's 999 Control Officers took 32 calls to the fire.
The Brigade was called at 1303 (Tuesday) and the fire was under control by 0051 (Wednesday), but crews will remain on scene throughout the day. Fire crews from Deptford, Greenwich, East Greenwich, Lewisham, Peckham and surrounding fire stations were at the scene, along with a number of support vehicles.
The fire is believed to have been accidental and caused by hot works being carried out on the roof.