Drivers face over four months of disruptions on the A702 from Monday as roadworks begin at Candymill.
And they are expected to last right through to the end of March next year.
Roads network body Amey has announced that essential maintenance will take place on the A702 Brownsbank Cattle Creep, 500m north of Candymill, outside Biggar on the Edinburgh road.
Amey said that the project scheme required a lane to be closed, with temporary traffic lights in operation 24/7 for the full duration of the work, which is scheduled to finish on Thursday March 30 2017.
Phase 1 of this scheme will improve the road safety barrier at this location and will be completed in the current financial year.
Phase 2 will improve the Brownsbank Cattle Creep and associated carriageway and will be completed in the next financial year.
The combined value of both Phases is £425,000 and will benefit around 5,000 vehicles using this route each day.
The scheme is being planned in consultation with Transport Scotland, Traffic Scotland, the emergency services, local bus operating companies, South Lanarkshire Council and adjacent landowners.
Drivers can find real-time journey information by visiting www.trafficscotland.org or via Twitter: @TrafficScotland
And they can report a problem on the network by visiting: http://scottishtrunkroadsse.amey.co.uk/report-a-problem/