Fifteen fire engines and around 100 firefighters were called to a fire on Church Lane in Brent.
Firefighters tackled a large fire at a shop with two floors of residential properties above, a significant part of a loft conversion and a range of garages behind the property were destroyed by the fire.
Station Commander Stephen McGhie said: "We worked tirelessly to prevent the fire from spreading to further properties.
"Firefighters will remain at the scene for the next few hours to dampen down the area. We advise people avoid the area as the road is closed in both directions."
The Brigade's Control Office took the first of over 70 calls at 1441 and mobilised crews from Stanmore, Mill Hill, Willesden, West Hampstead and other surrounding fire stations to the scene. The fire was under control at 1757.
The cause of the fire is under investigation.