A stretch of the A52 Sleaford Road in Boston will shut from Saturday evening to Monday afternoon.
A series of different roadwork schemes are due to begin on the road at 6pm on Saturday night and should take until 4pm on Monday (July 29) to finish.
As a result the road will close between Lister Way and Brothertoft Road – including the Carlton Road roundabout.
Traffic will be diverted along Fydell Street and Argyle Street.
Highways bosses say several planned works have been grouped together to minimise disruption.
Andy Wharff, Area Highways Manager, said: “Anglian Water and National Grid Gas need this road clear of traffic to complete essential maintenance works.
“The Highways Alliance has taken this opportunity to refresh the lines on the road and repair sections of the footpaths, subject to weather conditions.
“By carrying out this work in one operation it will prevent us from having to close the road again in the near future.”