The closure will be in place from 10pm on Saturday (April 6) to 5am on Sunday (April 7).
A contraflow diversion for southbound traffic will be in place via the east-bore tunnel.
The west-bore tunnel will remain open for northbound journeys.
Vehicles between 4.8m and 5.0m in height travelling northbound will be diverted via the M25 clockwise.
The Dartford Crossing is a large bridge and tunnel system that spans the River Thames and links Dartford in Kent to Thurrock in Essex via the A282 road.
