Eight fire engines and around 60 firefighters are tackling a fire at a waste transfer facility on Belinda Road in Brixton.
Around 70 tonnes of household waste inside a metal structure is alight. There are currently no reports of any injuries.
Station Commander Ken Spratt, who is at the scene, said: "Firefighters are working hard to bring the incident at the waste transfer site under control as quickly as possible.
"On-site machinery is being used to turn over the waste so that firefighters can access hot spots. This is likely to be a protracted incident with crews on scene throughout the evening.
"The fire is producing smoke in the vicinity and we're asking people to keep windows and doors closed and avoid the area where possible. There are road closures in place between Hinton Road and Loughborough Park".
The Brigade's Control Officers took the first of more than 30 calls to the fire at 1710 and sent crews from Brixton, Clapham, New Cross, Lambeth, West Norwood and surrounding fire stations to the scene.
The cause of the fire is not known at this time.