Health Minister Obadiah Moyo says the vaccination campaign, with help from the World Health Organization, is targeting more than 500,000 people between Wednesday and Sunday. Moyo says close to 1 million more people will be vaccinated starting next week.
The government says the outbreak has sickened more than 9,000 people mostly in the capital, Harare, since September.
Many fear a repeat of 2008 when cholera killed more than 4,000 people at the height of the southern African country’s economic and political problems.
Water and sewer infrastructure has collapsed, with raw sewage flowing freely in some Harare streets.
Recently elected President Emmerson Mnangagwa has vowed to fight the “medieval” disease.
Niger’s leaders are also scrambling to control a similar outbreak there.
Niger’s public health ministry says at least 68 people have died in a cholera epidemic that began in July.
The ministry this week said it has registered more than 3,690 cases of the disease, which is caused by contaminated food or water and can kill within hours if untreated.
The epidemic has spread in the central Maradi region and has also affected the northern Tahoua, eastern Zinder and southwestern Dosso regions.
The U.N. children’s agency and World Health Organization have estimated that only 37 percent of the population in the Maradi region has access to clean drinking water and only 10 percent has access to basic sanitation.
Niger’s heavy rainy season from June to September allows the disease to spread easily.