The restriction will be in place on Queen Victoria Road from Monday, 4th March while work is carried out to install a new cycle track, safer crossing points and signalised junctions.
Queen Victoria Road, with the Royal Victoria Infirmary and Newcastle University on either side, is a busy route for traffic and is well-used by people walking and cycling, including by visitors to St. James' Park.
Once completed, the new road layout, crossing points and junctions will help to make the area safer for people, particularly those on foot and on bikes.
The temporary one-way restriction during the works means that vehicles will only be permitted to travel northbound along Queen Victoria Road, between St Thomas' Street and Claremont Road.
Two-way traffic will still be permitted on part of Queen Victoria Road, under temporary traffic signals, between Richardson Road and the junction with St Thomas' Street.
Footpaths on either side of the road are temporarily signed as shared space for people walking and cycling.
People wishing to access the car parks at the Royal Victoria Infirmary will still be able to do so and will need to follow a signed diversion route if they are approaching from Claremont Road and Central Motorway. When leaving the RVI car parks, vehicles will need to turn left onto Queen Victoria Road.
Access to the Accident and Emergency Department, via Richardson Road, can also be reached via the signed diversion route if approaching from Claremont Road and Central Motorway.
Cllr Marion Williams, cabinet member for a connected, clean city at Newcastle City Council, said: "We are now moving on to the next phase of works to improve facilities for people walking and cycling on Queen Victoria Road.
"To ensure the work is carried out as efficiently as possible and with the safety of the public and our highways team in mind, the road will be one-way only for vehicles during this time.
"This is a busy route and a key access point for people travelling to the RVI and the Newcastle University campus, and we are giving advanced notice of the temporary one-way restriction so that people can plan ahead for their journeys."
People are urged to allow extra time or consider using public transport or other means of active travel during the works.
The temporary one-way restriction will be in place until the works are completed later this year. A further phase of work, incorporating the junction at Claremont Road, is expected to follow in 2025, with details to be confirmed nearer the time.