State Highway 1 south of Kaikōura will close for eight days from Sunday so contractors can reinforce areas at risk of slips.
The NZ Transport Agency (NZTA) said heavy rain over the past two weeks frequently closed the road.
Kaikōura would still be accessible from the south via Culverden and Waiau.
NZTA earthquake recovery manager Steve Mutton said loose rock and debris from 12 slips between Goose Bay and Peketa would be removed.
This would make the road more resilient over the winter, he said.
NZTA would provide emergency access as well as some access for people who live along the road.
It will reopen at 7am on 4 April.