Minister of Health Riek Gai Kok told reporters that 171 cholera cases have been confirmed in the outbreak, which began in crowded United Nations bases in the capital Juba and spread elsewhere in the city.
Tens of thousands of people have sought shelter in the UN camps during 18 months of civil war.
At least 167 people died with over 6,400 cases reported in an outbreak last year, which was later contained.
"After subjecting cases to laboratory tests it was confirmed that there is a cholera outbreak," Kok said, adding that the first case recorded was on June 1.
Stamping out cholera - transmitted through drinking water or eating food contaminated with faeces or dirty hands - poses an additional major challenge for the government and aid workers.
The World Health Organization (WHO) and aid workers are carrying out cholera vaccination campaigns targeting over 100,000 people "to prevent a potential large scale outbreak and prevent deaths," the ministry added.
Kok insisted health workers were better placed to tackle the outbreak than last year.
"The government is in a better position to prevent a potential large scale outbreak this year, largely because of pre-emptive measures undertaken with support from WHO and partners," he said.
Two-thirds of the country's 12 million people need aid, with 4.5 million people facing severe food insecurity, according to the UN.
Civil war began in December 2013 when President Salva Kiir accused his former deputy Riek Machar of planning a coup, setting off a cycle of retaliatory killings that has split the poverty-stricken, landlocked country along ethnic lines.
The conflict has been characterised by ethnic massacres, rape and the use of child soldiers.
"Anyone with severe watery diarrhoea should report to the designated treatment centre or nearest health facility," the ministry said in a warning.
"Wash hands with soap or ash after using toilets and latrines, before preparing food and after eating food, boil or disinfect drinking water with chlorine.
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