The section of the U173 Kenmore to Amulree road, through Glen Quaich, will be shut for 17 weeks from December 23.
Council bosses say there is a likelihood of danger to the public due to adverse winter weather conditions.
The winding mountainous route becomes treacherous when the temperatures plummet. Warning signs at the entrance advise drivers to seek alternative routes in winter conditions, but they’re often missed or ignored by travellers.
The 10.8-mile route is narrow, winding, and features several blind curves and summits. There are few passing places.
A five-mile stretch be shut off from a property called The Garrows to the junction with the Braes of Taymouth.
The route may be reopened occasionally when deemed safe by police and the local authority.
And emergency vehicles will still be able to use the route throughout the closure.
Perth and Kinross Council say the likelihood of “adverse weather conditions” affecting the road throughout the winter months is the reason behind the closure.
The Glen Quaich road is regarded as one of the most picturesque, and dangerous, in Perthshire.
Its highest point is said to be at a peak of more than 1,700ft.
A statement from the council said the local authority and police will allow use of the road “where weather conditions allow”.
The traffic restriction announcement added: “The Perth and Kinross Council as traffic authority, being satisfied that there is a likelihood of danger to the public due to adverse winter weather conditions, hereby prohibit all vehicular traffic on the following length of carriageway.
“The order will prohibit traffic on the U173 Glen Quaich from the property known as The Garrows (282551, 740247) to its junction with Braes of Taymouth (277496, 745014) a distance of eight kilometres or thereby.
“It is to be effective from December 23 2019 for a period of 17 weeks.
“Wherever possible, the order will be relaxed where weather conditions allow and in the opinion of Police Scotland and the traffic authority, permit passage.
“Pedestrian and emergency vehicular access to premises will be maintained.”
An alternative route will be via the C451, A827, A826 and A822.