Part of the A70 Lang Whang from Carnwath to Edinburgh is closing for resurfacing.
The work will take place from the B7008 Harburn Road to the A721 Carnwath.
The road will be closed to all vehicles for a period of 14 days from Monday, August 12, at 7am.
South Lanarkshire Council says that the alternative route will be clearly signposted.
It advises road-users to allow extra time for their journey.