Washingborough Road will be closed for up to five months from Monday 17 February.
The road closure will be from the entrance of the Anglian Water compound in the west to the rail bridge just past the bypass site.
This will allow for the final new bypass roundabout to be built, along with other essential works including lowering Washingborough Road by 1.5m and carrying out drainage, street lighting, kerbing and surfacing works.
Cllr Richard Davies, executive member for highways, said: "When the closure starts, we expect there to be significant disruption south of Lincoln, particularly on the B1188 between Branston and Lincoln.
"Because of that, we're asking drivers to leave extra time for their journeys.
"We're also encouraging people to consider using other modes of transport while Washingborough Road is shut, including catching the train from Metheringham into Lincoln, and vice versa if possible.
"To ease traffic on the roads, we'll be installing temporary CCTV cameras at the Branston junction so our traffic team can monitor the area and tweak the timing of the signals there and at the Washingborough Road/Canwick Hill junction if necessary.
"We'll also be installing temporary traffic signals at the end of Heighington Road to make getting onto Canwick Hill easier for people choosing to use this route.
"However, our advice to drivers is to follow the official diversion and avoid using Heighington Road."
The signed diversion route for normal vehicles will be via Church Hill / Canwick Road / Sheep Wash Lane / Branston Road / Station Road / B1188 Lincoln Road, and vice versa.
The diversion route for lorries will be via B1188/Lincoln Road to B1202 to B1190, and vice versa.
Please note a right-turn ban onto Heighington Road will be in place for drivers traveling towards Lincoln.
Cllr Davies continued: "This road closure is an essential part of getting Lincoln's eastern bypass built, and it's important for people to remember all the benefits the new road will bring once open later this year.
"This includes reduced congestion in and around Lincoln and a huge boost to the local economy."
The 7.5km Lincoln Eastern Bypass project is part-funded by a £50m Central Government capital grant and will improve Lincoln’s infrastructure, encourage growth, minimise traffic congestion and enhance the inter-city environment.
For the latest news on the Lincoln Eastern Bypass, visit www.lincolnshire.gov.uk/leb.