Parts of Bankside will be closed until June for flood defence improvement works.
A section of Wincolmlee between Wilmington Bridge and Air Street will be closed from January to June so the Environment Agency can continue with the essential repairs.
A diversion will be in place from Fountain Road to Bridlington Avenue, Beverley Road, Sculcoates Lane and Air Street.
Businesses along this stretch will remain open as usual.
Councillor Mike Thompson, portfolio holder for environment at Hull City Council, said: “Unfortunately this road closure is essential so that protection can be improved for more than 60,000 homes and businesses that are currently at risk of flooding from the River Hull.
“We understand that some motorists will be frustrated with this closure, however it is crucial that this work takes place.”
So far, more than 1,600m of new defences have been installed since work began in April 2017.
The £64m project, supported with £1m from the Humber’s Local Growth Fund allocation, will better protect more than 60,000 homes and businesses in the city.
For more information about the River Hull Defences project or the upcoming road closures, email RiverHullDefences@environment-agency.gov.uk.