Work is being carried out on the junction as part of road upgrade works ahead of building the giant Northampton Gateway freight terminal.
The M1 remains open but all four entry and exit slip roads to and from the main carriageway will be closed for 56 HOURS from 9pm until 6am on Monday (February 14).
The A45 will also be coned off from Grange Park as will the A508 Northampton Road towards the village of Roade, close to the new site entrance.
Diversion routes via Mere Way, the A43, A5 and junction 15A will be well signposted.
Winvic Construction started main infrastructure works for the 450-acre logistics hub next to junction 15 in January 2021. When finished the project is expected to bring around 7,500 jobs.
Northampton Town has warned football fans heading for the club's League Two game at Port Vale to make sure they use either junction 15A or junction 16 to access the motorway.
And bus operator Stagecoach says its X6 service between Northampton and Milton Keynes will be diverted through Wootton, East Hunsbury and Blisworth and not call at its regular stops on the A45.