James Stuart, a corn merchant from Rothes, builder and later owner of Macallan Distillery (1868-1886, see "Glenrothes"), constructed Glen Spey (initially a corn mill called Roslin Distillery Mill). After purchasing Macallan Distillery, he sold Glen Spey to London-based wine and spirits merchant W. & A. Gilbey for £11,000. This marked the first time an English company acquired a Scotch whisky distillery. In 1904, they built Longmorn Distillery. In 1962, Gilbey merged with Justerini & Brooks, another long-established London wine and spirits merchant that had achieved tremendous success in America with J. & B. Rare blended whisky. The new company was named I.D.V. Glen Spey's production capacity doubled in 1970. Two years later, it was sold to brewer Watney Mann, and in the same year was acquired by Grand Metropolitan. In 1997, Grand Metropolitan merged with Guinness to form what is now known as Diageo's U.D.V. Glen Spey has long been a key malt whisky for J&B blend. For a period, it served as the single malt brand for wine merchant Unwin. Until 2001, Glen Spey was bottled as a single malt by its owner U.D.V.

Glen Spey distillery keeps a low profile, tucked away on Rothes' main street beneath the surviving walls of the once-feared Rothes Castle. The castle dates back to the 13th century, hosting King Edward I of England in 1296. By 1309, it was in the hands of the powerful Leslie family, who became Earls of Rothes in the 16th century and briefly Dukes of Rothes in 1680 (a title that lasted only a year). In 1662, locals burned the castle and adjacent buildings to prevent them from harboring thieves. During the era of coal-fired direct heating and open-flame lighting, distilleries were frequently devastated by fire (see Talisker, Glenrothes, Glenlossie, etc.). Glen Spey itself suffered severe damage from a major blaze in 1920.