The collision happened earlier this morning, Sunday March 10, near The Dog & Partridge pub.
The road remains closed in both directions between the A616 (Flouch) and the A6024 (Woodhead).
South Yorkshire police are currently at the scene and report the incident involves two HGVs, one of which has overturned, and a car.
Highways England said motorists are being diverted on to local road and urged them to plan ahead if intending to use the Woodhead Pass and use alternative routes.
Those travelling further afield should consider using the M62 or A57 Snake Pass as a trans-Pennine route.
Police said that driving conditions were also difficult due to snow.