To secure a quality water source, the distillery was built on the grounds of Pluscarden Abbey, six miles west of Elgin. Not surprisingly, many illicit distilleries in the late 18th century operated on church lands—reportedly as many as 50—and the current distillery, built in 1824, stands at a site called Milton that was once the abbey's mill. After the Duff family purchased the land, the name was changed to 'Milton of Duff' and an old waterwheel was retained. The distillery was acquired by William Stewart (co-owner of Highland Park Distillery) in 1866; Thomas Yorke joined him in 1890, and the distillery was expanded in the mid-1890s, with capacity exceeding one million litres of pure alcohol. In 1936, Yorke sold the distillery to Hiram Walker, who had acquired George Ballantine & Company the previous year. Between 1974 and 1975, Miltonduff underwent modernization, with annual production reaching 5.24 million litres of pure alcohol, making it one of Scotland's largest distilleries. A visitor centre was also built around the same time but was soon closed. In 1986, Allied Distillers acquired 51% of Hiram Walker, completing full acquisition the following year. In 2005, most of Allied Distillers' whisky interests were acquired by Pernod Ricard, including Ballantine's and Miltonduff Distillery. Miltonduff is now operated by Chivas Brothers, a subsidiary of Pernod Ricard.

Prinknash was originally a monastery donated by Alexander II in 1230. In 1454, it absorbed the old Benedictine monastery of Ecton but was abandoned during the Reformation. Nearly 400 years later, it was donated by Colonel Clegg-Stewart to the Benedictine community at Prinknash; in 1948, monks moved in again and the buildings were restored. In 1974, it was elevated to abbey status. Between 1964 and 1981, 2 Lomond stills were installed at Miltonduff to produce Mosstowie single malt whisky. Lomond stills were invented in 1955 by Alistair Cunningham, chief chemical engineer for Hiram Walker. They have a very wide, fat neck with 3 rectifier plates, similar to those used in continuous stills. These plates can be rotated to change reflux and produce different whisky styles. When horizontal, reflux is maximized; when vertical, minimized. They can run fully or with water added, the latter also increasing reflux. Mosstowie spirit is lighter than Miltonduff. Miltonduff also housed the Allied Distillers' malt distillery technical center with labs, engineering, and warehouse offices. Chivas Brothers' northern operations headquarters is now located there. The lab moved to Glen Keith technical center. The fermentation CO2 extraction process was invented here. In the 1960s, Miltonduff pioneered a new method of heating the first wash still. Wash passes through heat exchangers (using hot water from condensers) and is heated to 75-80°C before entering the still. Once the still is full, another heat exchanger extracts the wash, heats it to boiling with steam. The boiling wash then returns via an expander as steam to heat remaining wash. This continues until distillation is complete.