The house was built in 1752 on historic lands formerly held by the Douglases of Drumlanrig and Scotts of Buccleuch. In the 18th century it passed into the hands of Sir William Douglas of Drumlanrig, then to Lord Hume. When the owner fell from royal favour, the estate was ceded to the Crown. In about 1826, William Chisholme, a member of the Selkirk branch of the family who made a fortune in Jamaica, bought back the estate and it remained in his lineage until 1871. At the end of the 19th century it was bought by a Mr Henderson, who added a wing, modernised the estate cottages, installed a new water system (including a hydraulic ram for supplying water), and built the approach road and bridge at Woodburn.
Following his death in the 1930s, the estate was bought by a Mr Bruce before being put on the market by his nephew two decades later. This led to large areas of the estate such as Parkhill and Woodburn Farms being auctioned off. Due to complicated property exchanges, deaths, and bankruptcies during the decade, Chisholme House was left without a resident owner and gradually fell into decay. Historic Scotland moved to list the site in March 1971.
Chisholme’s fortunes changed for the better in 1973 when it was taken on by an English educational charity, The Beshara Trust, to become a school and retreat centre.