Days of heavy rains brought on by El Nino have caused three major rivers to swell, and authorities have reported at least six weather-related deaths.
A state of emergency is in force in Paraguay, the worst hit nation, where 130,000 people have fled their homes.
In northern Argentina, some 20,000 people have left their homes.
Dry weather is forecast for the Brazil-Uruguay border region in the next few days, but in Paraguay and Argentina water levels are still expected to rise.
The Paraguay river in the capital Asuncion, is only 30cm (12in) away from overtopping its banks. Officials warn this could lead to widespread flooding in the area.
And it could also affect thousands of other people who live by the Paraguay - the country's main river - the authorities said.
"(The flooding) was directly influenced by the El Nino phenomenon which has intensified the frequency and intensity of rains," Paraguay's national emergencies office said.
Nearly 200 electricity pylons have been damaged or destroyed by strong winds, causing power cuts.
Four people have been killed by fallen trees.
After declaring the state of emergency, President Horacio Cartes said $3.5m (£2.3m) would be immediately available in relief funds for the victims of the flooding.
At least two people have died in the floods, which are mostly affecting the north-eastern provinces of Entre Rios, Corrientes and Chaco.
Some 20,000 people have been evacuated in the border city of Concordia, where the Uruguay river is now 14 metres (46 feet) above its normal levels.
Local officials said the flooding was the worst in the last five decades.
Newly-elected President Mauricio Macri is expected to visit the region later on Sunday.
In the southern Brazilian state of Rio Grande do Sul, nearly 1,800 families in almost 40 towns had been forced to leave their homes.
Heavy rain began to fall in the region on 18 December, swelling the Uruguay and Quarai rivers.
President Dilma Rousseff flew over the flooded region on Saturday to inspect the damage.
Thousands of people have been made homeless in the past few days, but most of them have now returned home.
The authorities warn that water levels are expected to remain at their current high level for several days before subsiding.