Contractors from Highways England are resurfacing a half a mile stretch of the westbound carriageway between the crossroads at Barton Hill to the junction with Foston Lane.
The work will be carried out between 8pm and 6am from Monday to Thursday this week. Temporary traffic lights will be in operation overnight and traffic will be restricted to 50mph.
From Monday 12 October, a half a mile stretch of the A64 will also be resurfaced between the villages of Crambeck and Huttons Ambo.
Temporary traffic lights will be in place between 7pm and 7am along with a temporary speed limit of 40mph. The work is expected to be completed on Tuesday 20 October.
Highways England project manager Sujad Hussain said:
When complete, this project will provide drivers with smoother and safer journeys along the A64.
The work will be carried out overnight when traffic levels are at their lowest to keep disruption to a minimum.
Members of the public should contact the Highways England customer contact centre on 0300 123 5000.
Journalists should contact the Highways England press office on 0844 693 1448 and use the menu to speak to the most appropriate press officer.