West Yorkshire Fire & Rescue Service confirmed that the crews were sent to the scene on Burnley Road at about 5.45pm.
The service initially sent four engines and one aerial appliance but increased numbers due to the scale of the fire.
At about 7.05pm, the fire service shared an update to say the fire was under control.
The statement said: "The mill fire in Burnley Road, Mytholmroyd, Hebden Bridge, is now under control and is well surrounded by firefighters.
"Police and council are dealing with traffic management due to closed road. Thank you for your patience."
By 8pm, the service informed the public on Twitter that the number of fire engines was being scaled back from 15.
The A646 between Mytholmroyd and Hebden Bridge was closed from 5pm as police and fire crews battled the blaze.
At about 6.55am today, police confirmed the major road remains closed as emergency services are still on the scene.
A spokesperson said: "Burnley Road through top side of Mytholmroyd is closed and emergency services still on scene and dealing with an incident from yesterday.
"Our log 1468 of yesterday refers. Share and make everyone aware. Quite a few 101 calls about this."
Metro Travel News tweeted this diversion information: "A646 Burnley Road closed due to a mill fire, 592 divert, towards Todmorden via Mytholmroyd, Cragg Rd, Turvin Rd, Rochdale Rd into Littleborough then right into Todmorden, diversion in BOTH directions."