The burst just to the south of the Clyde from the city centre at Bridge Street is causing widespread disruption.
People living as far apart as the Gorbals to Pollokshields, Shawlands, Mount Florida and south to Newlands on the fringes of East Renfrewshire have been experiencing disruption.
Scottish Water said it was working to restore supplies and the city council has closed a number of roads near the burst main to allow repairs to be carried out.
A spokesman said: "A burst water main has been located at Bridge Street, G5 customers here may experience loss of water supply, low pressure, and discoloured water.
"A squad will be on site shortly to carry out the necessary repairs and will restore supplies as soon as possible."
It later added that it was affecting the Glasgow G41, G42, G43 and G45 postcodes, covering the above areas.
He added: "We're working hard to complete repairs and apologise for the disruption to our services."
Residents took to Twitter to vent their anger at the lack of water supplies.
SirJeshi tweeted: And now, we have no water. Bravo Glasgow. I've had more bad luck in the last month and a half than in the last 23 years. And now, we have no water. Bravo Glasgow."
lucytweet1 tweeted: "There's no water in the southside of Glasgow. Sort it out @scottish_water - I smell."
LouMRobertson wrote: "Scottish water tells customers no ETA on repair to burst main affecting large area of Glasgow."
Neil Johnson tweeted a picture of flooding, adding: "If you're on the South-side of Glasgow and wondering why you have no mains water, this is why."
Daniel Gates tweeted: "No water to most of the southside of Glasgow!!!! How am I gonna keep going without tea? Get a move on @scottishwater."
Roads have been closed causing travel disruption over the Clyde, while the issue is being dealt with, the council said.
Glasgow City Council issued the following traffic bulletin: "The Glasgow Bridge is closed southbound to all traffic at Jamaica Street and Kingston Street is also closed between Centre Street and Bridge Street due to a burst water main at Bridge Street and Oxford Street."