The A57 Snake Pass will be fully closed from Monday, October 4, until Friday, October 15.
Derbyshire County Council says it will be carrying out roadworks to give the road “a bit of a spruce up” ahead of winter.
The closure will remain in place over the coming weekend – October 9 – 10.
A county council spokesperson posted on Facebook to say: “We’ll be doing some resurfacing, fixing potholes, replacing some drains and clearing others, replacing some signs, repainting road markings and carrying out some investigation work on one of the retaining walls.
“No traffic or bikes will be allowed through for safety reasons, although access still open for residents and farmers who need it.
“Apologies for the inconvenience, diversions will be in place.”
A diversion route will be in place for drivers via the A624, A6, A623, B6049, A6187, and A57.
Snake Pass is notorious for closing for an average of 70 days a year due to dangerous conditions brought on by bad weather.
The hazardous route is known for being filled with bends and blind summits that can catch unprepared drivers off guard.
There were 28 serious or fatal accidents on the road between 2017 and 2019, according to the Road Safety Foundation.
Auto Trader magazine named Snake Pass one of the best driving roads in England in 2009. It is lauded for its breathtaking views of the peaks and Manchester city at its summit.