Six fire engines and around 40 firefighters were called to a pub fire on Dartmouth Road in Forest Hill.
Most of the first floor and part of the roof of a pub were damaged by fire. Three people left the building before the Brigade arrived. A man and a woman were taken to hospital by London Ambulance Service crews.
The Brigade's Fire Investigators believe the fire was caused by the unsafe disposal of smoking materials.
Station Commander Verona Clarke, who was at the scene, said: "Road closures were in place whilst crews worked to make the scene safe and we asked people to avoid the local area.
"One of the Brigade's new 32-metre turntable ladders from Forest Hill Fire Station attended the scene.
"We’d rather you didn’t smoke at all, but if you are a smoker, it’s absolutely vital you ensure your cigarette is completely out when you’ve finished smoking it.
“If you don’t, you risk causing a fire which could not only destroy your home, but also cost you your life.
“This is also a reminder to never try to tackle a fire yourself. Leave it to the professionals. As soon as you become aware of a fire in your property, get out, stay out, close the door behind you and call 999.”
The Brigade was called at 0852 and the fire was under control by 0959. Fire crews from Forest Hill, Lewisham and Beckenham fire stations were at the scene.