Brixton Hill (the A23) is expected to be closed between Upper Tulse Hill and Brixton Water Lane until early next week because of a burst Thames Water main.
It is causing serious damage to the road as well as flooding in the area.
Thames Water says it is working on the main, but the road is expected to remain closed until early next week.
Local bus routes are on diversion.
Emergency gas works are also taking place on Brixton Hill.
Thames Water was last month fined £8.5 million for failing to meet its target to cut leaks from its mains and is being investigated by the regulator Ofwat for an “unacceptable failure” to control leakages, with 180 litres leaking daily from each property it supplies.
In July 2011 Brixton Hill was also closed by a burst water main and 50,000 local properties lost their water supply for 12 hours.
Research by the University of Greenwich shows water consumers in England pay £2.3bn more a year after privatisation than if water companies had remained publicly owned.
Work to repair another major burst main has been disrupting traffic in the Tulse Hill/West Norwood area for months.