South Australia State Emergency Service media officer John Merriman said a watch and act warning had been issued for low lying areas between Tailem Bend and Wellington about 100 kilometres from Adelaide.
Wellington sits north of the mouth of the Murray River before it flows into Lake Alexandrina.
"The alert was issued due to rapid river level rises which may result in properties becoming flooded or isolated, potentially trapping people without water power and other essential services," Mr Merriman said.
The SES advised people should evacuate to stay with family, friends or alternative accommodation in areas unaffected by flooding.
"If the situation worsens, it may not be safe to leave, and maybe too dangerous for emergency services to provide assistance," Mr Merriman said.
The warning came a day after Volunteering SA called on South Australians to support their Riverland neighbours by joining a volunteer agencies on the ground.
"We are in the midst of a declared major emergency that requires a coordinated approach to best help communities," Chief executive Hamilton Calder said.
"By signing up as a volunteer, we can ascertain how many people can assist during and after the unfolding flood disaster."
It is expected up to 4000 homes could be inundated, with about 1100 properties already flooded across the state.
Levee construction along the river is nearing completion, with the last works expected to be finished this week in towns including Mannum, Berri and Loxton.
A number of ferry services across the river have closed or been moved to higher ground.
The high-water mark is expected to hit Renmark, near the Victorian border, between Christmas and New Year and then reach Murray Bridge, east of Adelaide, by January 17.
The SA government has offered $51.6 million in assistance to tourism and other businesses, alongside direct emergency payments to homeowners.
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