Two motorists have died in an accident on the A17 at Sutterton, south of Boston, the first fatalities on Lincolnshire's roads in 2004
It is understood two vehicles were involved in the accident at around 0900 GMT on Monday.
Major diversions have been set up in the area, off the A17 at Bicker Bar, A52 at Gosberton and A16 at Algakirk.
The road is expected to remain closed for some hours while police examine the area and clear debris.
Last year 104 people died in road accidents in Lincolnshire.
A Lincolnshire MP is urging people to join a campaign to stop more people being killed on the county's roads.
The Conservative member for Gainsborough, Edward Leigh, wants the A15 between Lincoln and Scunthorpe widened to a dual carriageway.
He said people need to put pressure on the Government because the road is a death trap.