Hempstead Road is due to be closed at night for almost three weeks as part of a £1.1million resurfacing operation.
The main road will be closed between 8pm and 5am from Monday March 17 for the scheme, which is expected to last at least 19 days.
The work will be done in phases and resurface the road from the Hunton Bridge roundabout with the M25 to the town hall roundabout with The Avenue.
Hertfordshire County Council said the work schedule could change depending on the weather.
During the work, signed alternative routes will be in place and the council said vehicle access to properties will be maintained whenever possible along the road. Pedestrian walkways will not be affected.
Terry Douris, cabinet member for highways, said: "These works form part of Hertfordshire County Council's on-going commitment to maintain and improve our roads for the benefit of all road users in Hertfordshire.
"We appreciate that this is a major and busy route and understand that these significant resurfacing works are likely to cause disruption and inconvenience to motorists. We apologise for this and would ask everyone for their co-operation while the work is in progress."