Around 75 firefighters and 15 fire engines are tackling a blaze at a site that is believed to be a dairy.
London Fire Brigade warned that any gas cylinders inside the property could explode and erected a safety cordon in Wood Lane, Shepherd's Bush, west London.
Fire crews from across London tackled the flames after being called out at 9.35am. The fire brigade said later that the blaze had been contained but officers were likely to remain at the scene for some time. A gas cylinder is still being cooled down.
A spokesman said: "The fire is still going but it is contained. It is not over but we are making good progress."
The Metropolitan Police said it had closed the A40 in both directions in the area "so that the fire brigade can work safely".
More than 100 people were evacuated from the Unigate factory complex, according to a local petrol station worker.
Rashid Ansari, 23, a sales assistant at Esso in Wood Lane, said: "The fire brigade evacuated more than 100 people. The fire took place around the back of the Unigate factory. It is a multiple factory so a lot of people work there. It is a welding factory. They have closed the road and not a single person is allowed down here. There is lots of thick, dark smoke. The fire brigade have controlled the fire right now."
The cause of the blaze is not yet known.
A spokeswoman for Dairycrest said the company sold the building in 2002, but she did not know who bought it.
An ambulance and a hazardous area response team were in attendance but a London Ambulance Service spokeswoman said no one has been reported hurt.