No road, rail or air transport will be allowed until further notice, Mr Kenyatta said.
He declared Nairobi, Kajiado, Kiambu, Machakos and Nakuru counties to be “disease-infested zones.”
All in-person meetings in the counties have been banned.
International travel will continue on condition that all passengers present negative Covid-19 certificates.
The president has also increased curfew hours to now begin at 20:00 until 04:00 in the five counties, and revoked all special passes that allowed people to travel during the restricted hours.
The sale of alcohol in the areas has been banned and restaurants ordered to do only provide takeaways.
Kenya’s Covid-19 positivity rate has jumped from 2% to 22% between January and March.
The president said at least seven people are dying every day from Covid 19. In Nairobi, six out of 10 people test positive for Covid-19.
The new measures will come into effect at midnight.