The agriculture ministry said the movement of animals, people and vehicles at thousands of farms would be banned from 6:00 am (local time) on Saturday for disinfection.
A series of outbreaks of foot-and-mouth in recent months have resulted in the slaughter of around 25,000 pigs, and concern has grown as cases have spread to farms close to the capital Seoul.
The first cases were detected in July, only two months after South Korea was declared free of the disease at a meeting of the World Organisation for Animal Health in Paris.
In 2011 a devastating foot-and-mouth outbreak hit the entire Korean peninsula and resulted in the culling of nearly 3.5 million cattle, pigs and other animals in South Korea alone.
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The Seoul government estimated the cost of that outbreak at USD 2.6 billion.
Foot-and-mouth disease affects cloven-hoofed animals such as cattle, pigs, deer, goats and sheep.
The battle to contain foot-and-mouth has coincided with outbreaks of avian flu in poultry farms which have resulted in the culling of more than 500,000 birds in the past four months.