The A421 between the Eagle Farm roundabout and Junction 13 of the M1 will be fully closed from 10pm tonight until 6am tomorrow morning.
The stretch of road will reopen for the day tomorrow but close again from 9pm - and this time it will stay closed for the entire weekend - until 6am on Monday December 16.
The M1 will be open between junctions 13-14 so this can be used as a diversion. For a non-motorway route, motorists are advised to use the A422 diversion, which is signed.
They closures are to allow work to take place on Cranfield Bridge. Traffic will be switched to the new road surface so the existing carriageway can be levelled out, says MK Council.