Four fire engines and around 25 firefighters tackled a fire at a flat on Maryon Grove in Charlton.
A four-roomed flat on the third floor of the disused four-storey block was destroyed by fire. There were no reports of any injuries.
The Brigade was called at 0309 and the fire was under control by 0525. Crews from East Greenwich, Plumstead and Eltham fire stations attended the scene.
The fire is believed to have been accidental and the cause has been recorded as undetermined.