The £1.2million project will replace more than two miles of pipes in the East End and south of Glasgow to cut the risk of bursts and disruption to supplies.
About 12,000 people living in Shettleston, Tollcross and Mount Vernon will benefit along with 11,600 in Cathcart, Muirend and Newlands, 3000 in Bridgeton and Dalmarnock and 1000 in Denniston.
Some customers in the areas have experienced disruption to their supply as a result of bursts. Pipes in some parts of the network are 120 years old.
Jim Hassan of Scottish Water said: "We are delighted to be starting this key investment which will benefit so many of our customers in these parts of the east and south of Glasgow for many years to come.
"We are well aware of the inconvenience that burst water mains cause and a reduction in the frequency of bursts on our trunk-mains will reduce disruption to our customers and road users in the city."
The work, to be carried out for Scottish Water by contractors Farrans, is expected to take a year to complete.
It will begin in the Duke Street and Bellgrove Street area around October 29.
Traffic measures involving four-way traffic lights and a parking ban on the top section of Bellgrove Street will be in place at the junction of Bellgrove Street and Duke Street.
Work in the Gallowgate at its junction with Bellgrove Street will start around November 12 and take about three weeks.
Work will stop during Christmas and re-start in the new year, and progress to Millroad Drive, Shettleston Road and London Road in the East End and to Cathcart Road and Holmlea Road in the South Side.
Charlene McBride, Scottish Water's regional community manager, said: "There will be no disruption to supply to customers during this work.
"Our work will require some traffic-management in streets such as Bellgrove Street, London Road, Shettleston Road and Cathcart Road but we will do everything possible to minimise any disruption."