The torrential rain that started Saturday prompted mudslides and rubble to surge into the Maipo river which supplies most homes in the capital.
"We are talking about 1.45 million homes that are going to be affected by the cutting off of the water supply, which will be total or partial in 30 districts" of Santiago, the region's governor Claudio Orrego told a news conference.
He said the cut would therefore affect more than 60 percent of the city's 6.5 million-strong population -- about 3.9 million people.
The move prompted many people to go out with buckets and pans to collect water at emergency water taps made available by the authorities.
Others rushed to supermarkets to bag bottles of water from the shelves.
"We still do not know when the drinking water will be turned back on," Orrego said.
"We cannot guarantee resumption of the service until the River Maipo clears up."
Authorities ordered restaurants and businesses without drinking water to stay closed.
They also postponed the start of lessons for the new school term on Monday.
The interior ministry said four people were known to have died and six were missing due to the rain.
A rainstorm hit near the river in the countryside east of Santiago.
"The force of nature swept away bridges and left 1,200 people cut off" in Cordillera province, said the area's governor Vanessa Marimon.
The ministry said 3,300 people were cut off overall by floods.
Heavy rain also caused flooding in the northern Antofagasta region and in the tourist district of San Pedro de Atacama.
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