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The American Tobacco Company was founded in 1890 by J. B. Duke as a merger between a number of tobacco manufacturers including Allen and Ginter and Goodwin & Company. The company was one of the original 12 members of the Dow Jones Industrial Average in 1896.

Akin to the domination of Standard Oil in the same era, the American Tobacco Company dominated the industry by acquiring the Lucky Strike Company and over 200 other rival firms. The company built processing plants and warehouses in Reidsville, North Carolina and Durham. Antitrust action begun in 1907 against the American Tobacco Company, which broke the company into several major companies in 1911. Those companies include:

• American Tobacco Company
• R. J. Reynolds
• Liggett & Myers Tobacco Company
• Lorillard

The American Tobacco Company, which started acquiring a wide range of non-tobacco products during the 1970s and 1980s, renamed itself to American Brands in 1986^[1], which has since renamed Fortune Brands. American Tobacco became a subsidiary of American Brands for the next ten years until the company shed its tobacco brands to competitors.

The company's share in British American Tobacco (BAT) was sold at the same time. In 1994 BAT acquired its former parent, American Tobacco Company (though reorganized after anti-trust proceedings). This brought the Lucky Strike and Pall Mall brands into BAT's portfolio as part of BAT's American arm, The Brown & Williamson Tobacco Company. B&W later merged with R. J. Reynolds Tobacco Company in 2004.

American Tobacco left Reidsville and Durham in the late 1980s.

In 2004, the previously abandoned American Tobacco campus in Durham was reopened as a complex of offices, shops, and restaurants. Developed by Capitol Broadcasting and reopened as the American Tobacco Historic District, Phase 1 consisted of the Fowler, Crowe, Strickland, Reed, and Washington Buildings, and included the construction of two new parking garages and a water feature through the center of the campus. Phase 2, consisting of the remaining buildings at the north end of the site, is under construction as of late 2006.

The American Tobacco Trail, named for the company, is a multi-use rail-trail that begins just south of the Durham complex and runs 22 miles towards Chatham and Wake counties. It follows the route of a railroad that once served the factories, but was later abandoned when these facilities shut down.

In the golden age of radio, as well as early television, American was known for advertisements featuring a fast-talking tobacco auctioneer named L.A. "Speed" Riggs. His rapid-fire and song-like patter would always end with the exclamation, "SOLD, American!"

• Robert Sobel The Entrepreneurs: Explorations Within the American Business Tradition (Weybright & Talley 1974), chapter 5, James Buchanan Duke: Opportunism Is the Spur ISBN 0-679-40064-8
• Green vs. American Tobacco, The first case in U.S. history to find a Tobacco company responsible for the death of an individual.