The Ministry of Works and Transport says it is to facilitate renovation works on the Red House.
In a public notice on Friday the Ministry said the section of Knox Street adjacent to the Red House will be closed permanently under Section 38 of the Highways Act).
The closure will take effect from Monday November 6th 2017.
The Ministry said it apologises for the inconvenience caused and thanked the public for its cooperation.
Reconstruction of the Red House resumed last year after the project was halted following the discovery of prehistoric bones belonging to indigenous people underneath the building's foundation.
Government said the project, which is estimated cost approximately $400 million, is scheduled to be completed in 2018.