Part of the Heads of the Valleys road in Blaenau Gwent and Monmouthshire will be closed in both directions this weekend as the A465 upgrade continues.
The four-mile stretch between Brynmawr, at the A467 King Street roundabout, and Gilwern, the A4077 Main Road junction, will be shut from 20:30 on Friday.
It will re-open at 06:00 on Monday.
Motorists are being advised to take a diversion via Pontypool and Abertillery on the A467 and A4042.
The roadworks are part of the Welsh Government's £800m upgrade programme project which is scheduled to be completed in 2020.