Whalebone Lane will permanently close on Tuesday 30 August.
When complete, the new relief road will sever the local access road to enable the new carriageway to be constructed, connecting the A52 Somerby Hill roundabout to a new roundabout just east of the River Witham and East Coast Main Line.
A new junction will be created on the relief road to provide future access to Whalebone Lane.
Cllr Richard Davies, executive member for highways, said: "As part of the relief road project, we'll be stopping up Whalebone Lane at its A52 junction at the end of August.
“This will allow Galliford Try access to the area for completing the new section of relief road between Somerby Hill roundabout and the new mid-route development roundabout being built.
“Once closed, we will still be allowing access to the quarry until the new section of road is opened next spring.
“I know closing Whalebone Lane will no doubt cause some disruption for those who regularly use it, so I want to thank everyone for bearing with us as we continue building Grantham’s new relief road.”
The Grantham Southern Relief Road project is being led by Lincolnshire County Council and supported by South Kesteven District Council, Greater Lincolnshire LEP, Highways England, Department for Transport, Network Rail, Homes England and local businesses.
For the latest news on the Grantham Southern Relief Road, visit www.lincolnshire.gov.uk/majorprojects.