Highways England says it is intended to provide drivers with better and safer journeys.
Work will start between Crambeck and Welburn in March as part of a £22 million investment along the A64.
The four-month project will include widening the carriageway, creating right turn lanes, introducing five new traffic islands and footpath, and improving the layout of junctions.
Highways England project manager Chris Dunn said: “This vital work will improve safety for drivers using the A64.
"The improvements are part of our wider investment to enhance journeys and safety for the thousands of people who use this route every day.”
Most of the work will be done during the day, with narrow lanes and a reduced speed limit, although there will be some overnight closures and the use of overnight traffic lights.
Elsewhere on the A64, Highways England is installing ‘village gateways’ between Welburn and Staxton in March.
The gateways are characterised by features like ‘welcome to’ entry signs asking people to drive carefully, and the circular sign showing a lowered speed limit through the villages.
There will also be coloured road surfacing, lane narrowing and clear boundaries for drivers, as well as extra signage.
The work, due to run until the end of the year, includes extending the 30mph speed limit in Rillington, lowering the speed limit to 30mph in Sherburn, and to 40mph in Rillington Fields, West and East Heslerton, Potter Brompton, Ganton and Staxton.
The speed limit will come down to 50mph in Welburn and Crambeck, Huttons Ambo, Scagglethorpe, Scampston, and West and East Knapton.
The project, which has the support of North Yorkshire Police, follows a 2018 road safety study and is also being carried out in response to complaints from residents and campaigners along the A64.
Meanwhile, the ongoing work on pedestrian and cycling facilities between Staxton and Seamer to further improve safety along the route is due to finish this spring. Highways England is widening the footpaths, staggering crossing points, putting in improved signage and clearing vegetation.
Further information can be found by following @highwaysYORKS on Twitter, visiting HERE or by calling the Highways England on 0300 123 5000.