Motorists are being urged to avoid Junction 10 in Walsall this weekend where a stretch of the motorway is shut in both directions.
Traffic is being diverted off the carriageway at the exit slip road, up and over the junction and then back onto the motorway while 44 metre-long steel bridge beams weighing up to 120 tonnes are lowered into place.
It is the second time in two months the junction has been shut as part of a £78 million scheme to reduce congestion through the Black Country.
Work was carried out on the north bridge in August and now beams are being installed for the south bridge, with the motorway closed until Monday morning.
The southbound carriageway closed at 8pm on Friday evening, with the northbound closure delayed until 11pm due to West Brom playing QPR at The Hawthorns. Baggies fans have faced long delays getting to the ground in recent weeks, even without the M6 closure, due to changes to which roads are open near the ground.
Anyone who can stay away from Junction 10 over the weekend is being urged to do so with long delays on the motorway as well as congestion on nearby local roads.
Tailbacks of around 45 minutes were reported in both directions throughout Saturday morning.
People heading north or south from the Midlands, such as Aston Villa fans heading to Old Trafford for the Manchester United match, have been encouraged to use the M1 instead of the M6 and allow plenty of extra time.
Villa supporters have already faced disruption over this weekend's match due to the kick-off time being changed from 3pm to 12.30pm just two weeks ago, as a result of a Courteeners concert at the Old Trafford cricket ground.
Also on Saturday, Birmingham City are at home to Preston North End and Walsall are hosting Bristol Rovers. On Sunday, Wolves fans face a 160-mile journey down to Southampton.
And the disruption does not finish on Monday.
Once the beams are installed, the bridge deck panels will begin to be installed meaning the junction will be closed from 8pm until 6am Monday to Friday until October 20.
And on Saturday, October 9, the stretch of motorway will close at 8pm uintil 6am on Monday October, 11 so more of the panels can be lifted into place.
The same up and over diversion will be in place for every closure.