The eastern end of Heathcote Road will be closed on some weeknights from May 22 and for full weekends from about a month later.
Transport for NSW has updated previous advice on road closures with the start of work on upgrading the bridge over Woronora River at Engadine.
"Weeknight closures between New Illawarra Road and Princes Highway will be in place from Sunday 22 to Thursday 26 May between 8pm and 5am, weather permitting," a spokesman said.
"There will be more weeknight full closures to progress work on the project, and the community will be kept informed of the schedule.
"Full weekend closures from 8pm Fridays to 5am Mondays will be in place over the coming months with the first to start on Friday 17 June, weather permitting.
"During weekend closures, construction will be carried out 24 hours per day to reduce the need for set up and pack down, and to minimise the number of closures needed overall to safely deliver the project."
Transport for NSW expects there will be approximately eight weekend closures between June and September.
"During the weeknight and weekend closures of Heathcote Road, a detour will be in place via Kirrawee and the Bangor Bypass," the spokesman said.
"The detour is suitable for freight and B-double trucks up to 26 metres long but it may add up to 30 minutes to journeys, so motorists are asked to plan ahead and allow additional travel time.
"Transport for NSW recommends using alternative routes to reduce traffic congestion in the area where possible.
"Standard day work on the project will be carried out between 7am and 6pm weekdays and night work will take place between 8pm and 5am Sundays to Thursdays.
"There may be lane closures during these periods and traffic control will be in place to guide motorists at these times.
"Transport for NSW thanks the community for their patience during this time."
For the latest traffic updates download the Live Traffic NSW App, visit livetraffic.com or call 132 701.