The town-wide purge will be spearheaded by Middlesbrough Deputy Mayor Councillor Antony High and Executive member for Environment Cllr Dennis McCabe.
Under proposals to be considered by Middlesbrough Council's Executive, a 20-week programme will see every ward in the town targeted in succession.
Over the coming month all repairable potholes will be inspected, with a dedicated, skilled team assigned to the repair programme.
One week will then be allotted to each of Middlesbrough's 20 wards, with back-up provided by experienced highways staff as required.
Deputy Mayor Antony High said: "Now the worst of the winter weather is behind us, the time is right to sort out our roads once and for all.
"Potholes are a costly menace for drivers and cyclists, and they shouldn't have to put up with them.
"For the first time we're going to do a full audit of every pothole in the town, and then fix as many as we can in a single 20-week programme.
"I know that's something residents will welcome, and it should enable us to manage the problem more easily in future."
Councillor Dennis McCabe, Executive member for Environment, said: "This is a great initiative which I know will have a lot of support from the public.
"I'll be proactively involved in ensuring this approach continues well beyond the initial 20-week programme."
Subject to Executive approval, work is expected to start in April.
Middlesbrough Mayor Andy Preston added: "Everyone is sick of potholes across Middlesbrough.
"This action marks the start of improvement - finally."
A report on proposals to tackle potholes across Middlesbrough will be considered by the Council's Executive in March.