The historical origin of the brand is not entirely clear. By some accounts, the brand was founded by Rufus Mathewson Rose and was probably named in honor of him, his brother Origen, and their two sons. However, several different stories have been told about where the name Four Roses comes from. The current brand owners do not mention Rufus M. Rose in their version of the history, and refer instead to a man named Paul Jones, Jr, as the founder of the brand. The company says the brand name was trademarked in 1888 by Jones, who claimed it had been produced and sold as early as the 1860s. The Lawrenceburg, Kentucky distillery was built in 1910 in Spanish Mission-style architecture and is listed on the National Register of Historic Places.

The brand was purchased by Seagram in 1943. It was the top selling brand of bourbon in the United States in the 1930s, 40s and 50s. Around the end of the 1950s, despite the popularity of the brand, Seagram decided to discontinue the sale of Four Roses Bourbon within the United States in order to focus on sales of blended whiskey, although they introduced other brands of straight bourbons in the 1960s and 70s such as Benchmark and Eagle Rare. Four Roses Kentucky straight bourbon marketing was shifted to Europe and Asia, which were rapidly growing markets at the time. In these markets, it became the top selling bourbon. In the United States during this period, the Four Roses name was used on a blended whiskey, made mostly of neutral grain spirits and commonly seen as a sub-par rotgut brand. Four Roses continued to be unavailable as a straight bourbon in the US market for more than forty years until the brand ownership changed in 2002 after Seagram was purchased by Vivendi, and then sold most of its brands to Diageo, which sold the Four Roses brand to Kirin, who discontinued the sale of blended whiskey to focus exclusively on Four Roses Kentucky straight bourbon whiskey.