Eight fire engines and around 60 firefighters were called to a flat fire on Deacon Street in Elephant and Castle.
Part of a four-roomed flat on the 18th floor of the building was damaged by fire. There were no reports of any injuries.
Station Commander Dave Hill, who was at the scene, said: "Firefighters worked incredibly hard to bring the fire in Elephant and Castle under control.
"Crews evacuated residents on three floors of the building who were affected by smoke.
"The Brigade's drone team assisted by providing an aerial view of the incident.
"Road closures were in place causing heavy congestion. Firefighters remained on scene throughout the afternoon and we encouraged people to avoid the area."
The fire is believed to have been caused by the unsafe disposal of smoking materials.
The Brigade was called at 1058 and the fire was under control by 1215. Fire crews from Lambeth, Dockhead, Dowgate, Brixton and surrounding fire stations attended the scene.