The president was speaking to the nation about the growing threat of the disease that is multiplying in the country rapidly.
"This is a decisive measure to save millions of South Africans from infection and save the lives of hundreds of thousands of people", he said. This includes stores which sell food.
There will be provision for essential transport of staff and patients.
Individuals will not be allowed to leave their homes except under strictly controlled circumstances, such as to seek medical care, buy food, medicine and other supplies or collect a social grant.
Ramaphosa is expected to elaborate on the release of an economic stimulus package aimed at relieving the fierce financial pressure felt by businesses and citizens alike.
Other measures announced were that global flights to Lanseria worldwide Airport have been suspended, and tourists from high-risk countries will be confined to their hotel rooms.
Ramaphosa said temporary shelters that meet the necessary hygiene standards will be identified for homeless people.
A week ago, there were over 160,000 cases worldwide.
Ramaphosa called on everyone to act in the best interest of the country, not themselves; and said anyone caught selling goods at excessively high prices or involved in corruption or otherwise profiteering during this time, will be arrested and prosecuted, and jailed.
The lockdown will come into effect on Thursday night and be enforced by the police and the army, Ramaphosa told the nation.
The President applauded the commitment from the Rupert and Oppenheimer families who have donated over R1-billion each for small businesses and their employees to help cope during the tough times ahead.
The tourism sector, which is particularly hit hard by the new regulations, will also be supported.
Ramaphosa cited the success of similar lockdowns in Singapore and South Korea for implementing the lockdown.
Addressing the nation on the day that infections of the COVID-19 virus in South Africa increased to 402 - an increase of 128 in only 24 hours - Ramaphosa said immediate action was needed in order to avoid the country's fragile health system from becoming overwhelmed.
The move comes on the day the country announced that its confirmed cases had shot up to 402 from 274 cases the day before.
According the Ministry of Health, most of the cases are in the Northern Cape province.
The president added that while South Africa was indeed experiencing a harsh period of crisis and uncertainty, the unified approach to combatting the spread of COVID-19 was something to be proud of.