The distillery was founded in 1757 and, by 1798, was in the hands of Matthias McManus, whose son was executed in Mullingar due to the part he played in the United Irishmen rebellion of that year.
John Locke took over the distillery in 1843, and it passed down to his granddaughters Mary Evelyn and Florence Emily in 1943. The economic depression of the 1920s and 1930s took its toll on Locke's. In 1947 it was put up for sale and the successful bidder, the Transworld Trust, involved fraudsters from Switzerland and Austria. Oliver J. Flanagan alleged under Oireachtas privilege that Fianna Fáil politicians were linked to the deal; a tribunal of inquiry discounted the allegations but the damage contributed to Fianna Fáil's defeat in the 1948 election. On 19 March 1954 production ceased at the distillery. It closed completely in 1957 and the building began to fall into disrepair. Twenty five years after its closure, the community of Kilbeggan restored the distillery and opened it to the public as a whiskey distillery museum. Cooley Distillery bought the license to produce Kilbeggan and Lockes Whiskey, and later took over the museum along with opening a new working distillery in Kilbeggan.
Today the distillery is known as Kilbeggan Distillery, and includes a restaurant, The Pantry Restaurant, and a 19th-century waterwheel that is in working condition. The distillery can also be powered by a steam engine, which is in working condition but rarely used. It was installed to allow the distillery to continue operating in times of low water on the river.
Whiskey production recommenced in 2007, the year in which the distillery celebrated its 250th Anniversary. One of the two Copper Pot Stills that is being used in Kilbeggan was made in the early 1800s and is the oldest working Pot Still producing whiskey in the world today. It was once used in the distillery in Tullamore. In 2010 Kilbeggan became a fully operational distillery once again, with the installation of a mash tun and fermentation vats. Although the whiskey now in production at Kilbeggan will not be ready for sale until 2014, the three brands associated with the distillery—Kilbeggan, Locke's Blend and Locke's Malt—have, for many years, been made at the Cooley Distillery in County Louth from where they are transported to Kilbeggan to be stored in a granite warehouse over 200 years old. In late 2009, the distillery released small '3-pack' samples of its still-developing new make spirit at 1 month, 1 year, and 2 years of age. (In Ireland, the spirit must be aged a minimum of three years and one day before it can legally be called whiskey.)
The distillery's visitor centre was among the nominations in Whisky Magazine's Icons of Whisky visitor attraction category in 2008.