Traffic heading south will be funnelled into one lane near Junction 14 for Stafford on two occasions while National Highways strengthens the carriageway.
The first is between 9pm tonight and 6am on Saturday, with the second running from 9pm on Sunday to 6am on Monday.
From 6am on Saturday to 9pm on Sunday two lanes will be open to traffic, before all four lanes are reopened by 6am on Monday.
The lane closures are part of upgrades being carried out on a 17-mile stretch of the M6 between Junction 13 at Stafford and Junction 15 near Newcastle under Lyme and Stoke on Trent to make it a smart motorway.
A spokesperson for National Highways said: "To minimise disruption, we’re limiting the length of roadworks that we need for this work; however, we will need to close some lanes for limited periods of time.
"Please bear this in mind when planning your journeys, we're sorry for any disruption this may cause.
The M6 between Junctions 13 and 15 is one of the busiest sections of road in the UK, used by over 127,000 vehicles per day and suffers from heavy congestion and unpredictable journey times, especially during peak periods.
The scheme hopes to reduce congestion, remove major bottlenecks and improve journey time reliability which will help businesses in the area to be more efficient.