Snow ploughs and are attempting to clear the A628 Woodhead Pass this morning in a bid to get traffic moving again.
Gritters are also working on the road, which is blocked by snow and ice between Tintwistle and Flouch.
The M62 is also closed to traffic heading towards Manchester.
A number of vehicles were stranded there overnight.
Highways England said South Yorkshire Police officers are also at the scene to prevent motorists from trying to drive across the Pennines.
A spokesman said: "Please do not travel unless essential."