Around 75 firefighters and 15 fire engines were tackling a blaze at a site that is believed to be a dairy today.
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 were attempting to put out the flames after being called out at 9.35am.
The Metropolitan Police said it had closed the westbound A40 near the area.
A London Fire Brigade spokeswoman said: "There might be some gas cylinders inside the building.
"We have put up a temporary safety cordon as gas cylinders can explode when hot."
The fire brigade posted a photograph on Twitter at around 10.30am showing a large amount of thick, dark grey smoke, with the message: "Photo of smoke from Wood Lane fire live from the scene."
More than 100 people have been 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.
The "challenging" blaze is now being tackled by 75 firefighters and 15 fire engines, according to London Fire Brigade.
Station manager Rod Horton, who is at the scene, said: "The fire is affecting a range of industrial buildings on the dairy site.
"It's a challenging and developing incident at the moment and we're likely to be at the scene for some time."
An ambulance and a hazardous area response team is in attendance but a London Ambulance Service spokeswoman said no-one has been reported hurt.
A police spokesman said the A40 was now closed in both directions "so that the fire brigade can work safely".
Eastbound the road was closed from Savoy Circus and westbound from Gloucester Terrace.
Wood Lane was also closed south of Du Cane Road and Shepherd's Bush Lane was closed northbound towards the A40.
A Transport for London spokesman said: "Due to a building fire in the Wood Lane area, the A40 is currently closed in both directions between Savoy Circus and Marylebone Road, and the A3220 West Cross Route is closed both ways between the Holland Park Roundabout and the A40 Northern Roundabout.
"Buses are currently on diversion and TfL is working to divert traffic away from the area and minimise any disruption caused by this incident."
Firefighters said a gas cylinder had been found at the site and they were working to cool it down.
A post on the fire brigade's official Twitter page said: "We've found one acetylene cylinder at the site of the Wood Lane fire. Crews are currently cooling it to make it safe."
The fire brigade said later that the blaze had now been contained but officers were likely to remain at the scene for some time.
The 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."