The distillery was set up by John Cumming, who had previously been a whisky smuggler, in 1824. The distillery was sited high up on Mannoch Hill, above the River Spey due to the peat softening the water. The distillery started as farm distillery working on a seasonal basis after the harvest had been gathered. The distillery was mainly run by his wife, Helen Cumming, who used to sell bottles of whisky to passers-by through the window of their farmhouse.
In 1885 the distillery was rebuilt on a new piece of land but continued to stay in the hands of the Cummings, being run by Elizabeth Cumming, the daughter-in-law of Helen Cumming. The stills from the old distillery building were sold to William Grant who set up Glenfiddich distillery. The new building and stills meant that Cardhu could produce triple the amount of whisky it had previously produced. These higher production levels lead to Johnnie Walker and Sons buying much of Cardhu's output to put into their increasingly popular blend.
In 1893 Elizabeth Cumming sold the distillery to Johnnie Walker and Sons on the condition that the Cumming family could continue the day to day running of the distillery. Cardhu distillery kept working under these conditions until the onset of the Second World War when wartime restrictions meant that it was harder to use barley for distilling purposes.
In 1960 the distillery's still-house, mash-house and tun-room were rebuilt, and in 1970 steam coils were introduced to heat the stills and the number of stills was increased to six. Spring water from Mannoch Hill started to be mixed with water from the local Lynne burn to supply the increased production of the distillery.
In December 2003 Cardhu caused controversy by halting the production of their single malt and replacing it with a vatted malt which they called a pure malt in order to keep up with the ever-increasing demand for the whisky for use in Johnnie Walker blended whiskies. However, in 2006 Cardhu recommenced producing a single malt as the sales of Cardhu single malt dropped substantially due to the change.