More than 50 firefighters are battling the inferno, thought to be raging through the Unigate dairy warehouse in Wood Lane.
London Fire Brigade (LFB) said ten fire engines were dispatched to the site at around 09:35 GMT.
This has now been upgraded to 15 engines and 75 firefighters.
The cause of the blaze is unknown.
One eyewitness told the BBC: “You can see thick bellowing smoke”.
At 10:15 GMT, LFB said: “The fire is still very much ongoing”.
It added that it thought the fire was at “a range of industrial units” believed to belong to Unigate Dairy.
Police have closed Wood Lane in both directions, between Ariel Way and the A40. White City Tube station is also shut.
Traffic tailbacks stretch 4 miles up to Askew Rd at the junction with Uxbridge Road, and there is gridlock around Shepherd’s Bush Green.
Ambulance vehicles are on the scene, but no casualties have been confirmed.
