Le Grand Bouet in St Peter Port will be closed for five weeks starting from next Tuesday (3 September).
It is for the final phase of essential lining works on the sewer.
Guernsey Water carried out investigations earlier this year which confirmed that the sewer was in poor condition.
The road was then closed for three weeks so a new manhole could be installed, which provided access for this lining work to take place.
The lining works will be carried out in three sections, each measuring a length of 100-150m. Each section will need to be cleaned before the connections are checked by a robotic unit, the liner inserted, cured in place and finally the original connections are re-cut by the same robotic unit.