National Highways says the motorway will be coned off southbound at junction 15 at 9pm on Friday and reopen at 6am on Monday.
Diversion signs will take traffic off the motorway through Roade via the A508 towards the A5 and A509 to rejoin the M1 at Milton Keynes but drivers heading towards London are being encouraged to plan ahead and use alternative routes such as the M40, A1 or A14 and M11.
Programme manager, Lynne Stinson said: “Safety is always our top priority, and this is a significant piece of work which means we have to close the road to keep our teams and motorists safe.
“We’d encourage drivers to familiarise themselves with the diversion route before setting off and to leave additional time for their journeys. We’d also remind them to follow the signposts for the diversion and to avoid using sat-navs to help keep traffic flowing.
“It’s also important to ensure that people check their vehicle before setting off on their journeys.
“Simple things like checking fuel and oil levels, tyre pressures and that all lights are working properly, can keep everyone moving and the network flowing.”
The motorway will be closed to ensure the safety of engineers working on the carriageway to adjust the profile of the road as part of the smart motorway upgrade but teams will also be installing bridge joints at Cattle Creep emergency turn around, near Hartwell, and reconfiguring the road layout at Newport Pagnell Services exit slip road.