Twelve fire engines and around 80 firefighters tackled a fire on George Street in Marylebone.
The roof of a six-storey office block under refurbishment was alight. Several solar panels were also involved. A 32 metre turntable ladder has been in use and the Brigade's drone team have been assisting by providing an aerial view of the incident. There have been no reports of any injuries.
Although the fire has been brought under control, some road closures are likely to remain in place by the junction of George Street and Baker Street.
Station Commander Chris Young, who is at the scene, said: "Crews have been working in challenging conditions but have made good progress extinguishing this fire.
"Although most of the fire is now out, we are likely to remain at the scene for a number of hours damping down and ensuring the scene is safe. We would ask that drivers continue to avoid the area and find alternative routes."
The Brigade was called at 1809 and the fire was brought under control by 2152. Crews from Euston, Soho, Chelsea, Paddington, Kensington and surrounding fire stations attended the scene.
The cause of the fire is under investigation.