A short section of the A1032 Acklam Road, from the West Lane area heading south towards Linthorpe and Whinney Banks, will be closed to traffic in both directions from Wednesday.
The closure is part of the council’s resurfacing programme which has seen a number of roads closed for improvement work, including Marton Road.
Work will take place from 7.15pm to midnight on March 13, 14 and 15 and at the same times on March 18, 19 and 20.
The sections of road will be closed in three phases from the junction with Ayresome Street to the roundabout at Kingsbridge Crescent and Westbourne Park.
Road users are being urged to plan their journeys ahead and consider alternative routes where possible.
A local diversion route will be fully signed, with temporary bus stops where necessary.
A Middlesbrough Council spokesman said: “These works are part of a wider programme of resurfacing to improve roads across Middlesbrough.
“They have been planned to avoid the evening rush hour but some disruption to road users is inevitable and we apologise for any inconvenience caused.”