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
Nominations are now open for the 2017 ITV Fundraiser of the Year – part of the Daily Mirror Pride of Britain Awards.
Speed cameras across Scotland raked in more than £5 million over 2016, the highest since 2014.
Winners at this year Cumbria Tourism awards have been commended for their contribution to the county's tourism and hospitality industry.