Larch trees at Arduaine Garden in Argyll, which was saved from closure by public donations of almost £2 million, have to be chopped down after sudden oak death (so-called because it killed oak trees in California) was discovered.
The National Trust for Scotland (NTS), which owns the 20-acre garden, will start the felling process in autumn and said hundreds of trees will be axed to stop the problem spreading.
The disease, officially known as Phytophthora ramorum is a fungus that kills trees and shrubs, and had been previously found in the garden's shrubs, particularly rhododendrons for which Arduaine is famous. But it was spotted in a larch tree for the first time last autumn following aerial surveillance by the Forestry Commission.
That tree was felled and phytophthora identified. As a result, the Trust is required to fell surrounding larches to prevent the disease affecting an area where there are large commercial forest plantations which would be susceptible.
This poses a considerable problem in the hillside garden where there are no access roads and where important, rare shrubs grow underneath the tree canopy.
Maurice Wilkins, the head gardener at Arduaine, which lies on a promontory between Lochgilphead and Oban, said: "From a rough count, we have about 1000 larch trees and we will have to fell hundreds. We will make sure a lot of the best specimens are very carefully looked after even if we have to damage other things. But this will cause quite a bit of damage."
He has until January 2014 to remove or kill the trees required to comply with the order.
Mr Wilkins said: "We are allowed to kill the trees by removing rings of bark and leave them standing but we could not do that and open the woodland garden to the public, so we will have to fell and remove them.
"Ideally we would do that by helicopter but that would depend on cost. This situation in a garden is a new one for the Forestry Commission, so what we do here may provide a model for other places in the future."
Phytophthora ramorum and its relative Phytophthora kernovae have been spreading up the west coast of Britain for some years, as a result of the climate becoming warmer and wetter, and has affected larches in Cornwall and Wales.
It has now been found on juniper trees in the north of England, causing fear it could spread north to what is an important native species in Scotland.
The Trust had planned to close Arduaine and 10 other properties in 2009 as a result of a financial shortfall.
That galvanised a public campaign that led to a rethink and eventually an overhaul of the way the Trust is run.
Six months ago, the Trust announced the future of the garden was secure thanks to donations from members and charitable organisations amounting to £1.9m and a partnership with the neighbouring Loch Melfort Hotel.
Donors have now received letters from the Trust explaining the new threat but emphasising its long-term commitment to the future of Arduaine and that visitors will see little change during the spring and summer.
Mr Wilkins added: "What makes Arduaine special is that almost our entire canopy is Japanese larch. It was an inspired choice by Arthur Campbell in 1898 because you get more light in winter and lovely spring and autumn colour. He wasn't to know about phytophthora.
"We have to go ahead and be positive, and it will give us an opportunity to extend the range of plants in what has always been a plant-hunters' garden.
"In the meantime, there is no reason not to visit because felling won't start until autumn."