Diversions are in place to allow emergency services to deal with the crash on the A66 at Threlkeld, near Keswick.
Travelling towards west Cumbria, motorists are advised to use junction 41 of the M6, travelling along the B5305, Wigton.
Travelling towards Penrith, motorists should follow the diversions in place at the Crossthwaite roundabout, Keswick.
Cumbria Police say that the road will be closed for some time.
More top news
Firefighters, police, mountain rescue teams and an RAF helicopter have been searching for a man in the River Esk in Longtown.
A mixed picture over the next few days - summer is here, but there's a price to pay.
Staff at a Borders engineering firm in Kelso have been sent home after being told it has gone into liquidation.