Arthur I. Appleton made his fortune in business and spent it on art, racehorses, and marble. In the mid-1970s, he and his wife, the former film actress Martha O'Driscoll, bought land in the Ocala area and established Bridlewood Farm, a thoroughbred breeding and training facility. Ocala styles itself the Horse Capital of the World, and the Appletons fit right in. But Arthur had grander ambitions for the region. The City of Ocala donated a 44-acre site, and construction began in 1984. Working with Tampa architect Dwight Holmes, Appleton specified travertine marble imported from Italy for the exterior and Bolivian Capao Bonito granite for the floors. More than 300 tradesmen from 130 companies assembled the building, with glass from Pilkington of England and stonework by Antagon/Paleni of Montreal. When it opened to the public in 1987, rural Florida had a museum that could rival institutions ten times its city's size.

The permanent collection sprawls across seven major areas, each reflecting a different thread of Appleton's eclectic taste. The Equine collection honors Ocala's horse heritage with artifacts spanning over 3,000 years, from Eurasian Steppe Bronze Age bridle bits to contemporary equestrian art. European galleries cover the 17th through 19th centuries, with paintings and sculpture from the Romantic, Realist, and pre-Raphaelite movements. The Asian collection is one of the museum's largest, holding Tang Dynasty ceramic horse figures, rare celadon funerary vases, Chinese Export porcelain, Japanese netsuke miniatures, Meiji-era bronzes, and embroidered kimonos. Pre-Columbian galleries display ceramics, gold work, and jade from Maya, Wari, Moche, and Chimu cultures. The breadth is staggering for a museum in a city of 65,000 people.

The African art collection carries a provenance story rarer than most. Arthur Appleton purchased much of it from the estate of Dr. Victor David DuBois, who assembled it during years of government work across the continent. DuBois acquired many pieces directly from the artists and communities that created and used them, lending the collection an authenticity that auction-house purchases cannot match. Among the standout works is a 20th-century Dance Headdress with Hare Crest, called a Sibondel, created by the Baga people of Guinea. A full set of Maiden Spirit Dance Regalia from the Agbogho Mmuo tradition of the Igbo people of Nigeria commands its own display. These are not decorative curios; they are sacred objects of living cultures, and the museum treats them accordingly.

Arthur Appleton served in the United States Navy during World War II, and his Maritime Art collection reflects a sailor's eye for the sea. Paintings of historic sailing ships by British artists William Adolphus Knell, Richard Brydges Beechey, and Montague Dawson line the walls alongside detailed ship models. The Modern and Contemporary galleries pivot sharply forward in time, featuring works by Salvador Dali, Andy Warhol, Robert Rauschenberg, James Rosenquist, and Alexander Calder. Auguste Rodin's sculpture shares space with Whistler, Bouguereau, and Louis Comfort Tiffany. In 1996, the Edith-Marie Appleton Wing, funded by Arthur's sister, expanded the museum, and a dedicated art storage facility followed in 2009, bringing the total footprint to just under 82,000 square feet. Since 2004, the College of Central Florida has governed the museum, ensuring that Appleton's unlikely gift to horse country endures.