Motorists have been told to avoid Junction 10, for Wolverhampton and Walsall, as work continues on installing a new four-lane bridge.
The stretch will be closed in both directions from 8pm on Saturday until 6am on Monday – with people warned of delays and diversions.
It marks the third time the route has been shut over a weekend after it was closed off in August and September due to the improvement scheme.
Two new bridges are being built to replace the 50-year-old bridges currently in place, with the new wider structures introduced to tackle congestion at the busy Walsall junction.
Work was successfully carried out on the north bridge in August and the 44m-long steel beams were lifted into place for the south bridge late last month.
The bridge deck panels now have to be installed. The road closure this weekend will enable over half of the bridge deck panels to be put in place over the beams.
Traffic will follow an ‘up and over’ diversion at Junction 10 which will leave the motorway at the junction, travel over the roundabout and then re-join the M6 on the other side
And the M6 will also close between the exit and entry slip roads at Junction 10, between 8pm and 6am, every week night – Monday to Friday – until October 20 whilst the remaining panels are installed.
The transformation of the junction will double the number of lanes around the bottleneck junction from two to four.
National Highways, formerly Highways England, and Walsall Council, supported by the Black Country Local Enterprise Partnership, have joined forces to fund the upgrade.
Contractor John Sisk & Son is carrying out the work.
To help minimise disruption during the closure, motorists wishing to travel north or south are being advised to use alternative routes such as the M1. The old bridges will be demolished later in the scheme.
For traffic updates, follow HighwaysWMids on Twitter.
The National Highways 24/7 customer contact centre team can also provide information on 0300 123 5000.