Work will take place on the stretch of road between the Whitemare Pool and Lindisfarne roundabouts in mid-July and is expected to last until early 2022.
These will include full signalisation of the Mill Lane roundabout, realignment of the carriageway at one-lane pinchpoints and increasing stacking capacity at the Whitemare Pool roundabout.
South Tyneside Council says the work aims to cut congestion and improve safety.
Cllr Jim Foreman, Lead Member for Housing and Transport, said: “The A194 is a key gateway and commuter route in and out of South Tyneside.
“We, in consultation with Highways England, have identified the need for improvements to the carriageway and junctions along a stretch of the road.
“These will help traffic flow, cut journey times and congestion, enhance safety and improve air quality, as well as increasing the efficiency of the wider road network.
“Disruption will be minimal as two lanes will remain open where possible, with any necessary lane closures carried out overnight. We thank drivers in advance for their patience.”
Work will also see drainage, safety barriers and street lighting upgraded and the road will be resurfaced.
Signalised crossing facilities for pedestrians, cyclists and horse riders will also be introduced.
Residents living in the vicinity will receive a letter about the scheme.
Cllr Foreman added: “Investing in the built environment is one of the council’s core priorities, and we will continue to deliver major infrastructure schemes such as this to support economic growth.”