Louisville (usually ; see Pronunciation below) is Kentucky's largest city. It is ranked as either the 17th or 27th largest city in the United States depending on how the population is calculated (see Nomenclature, population and ranking below). The settlement that became the City of Louisville was founded in 1778 by George Rogers Clark and is named after King Louis XVI of France. Louisville is famous as the home of "The Most Exciting Two Minutes in Sports": the Kentucky Derby, the widely watched first race of the Triple Crown of Thoroughbred Racing.

Louisville is situated in north-central Kentucky on the Kentucky-Indiana border at the only natural obstacle in the Ohio River, the Falls of the Ohio. Louisville is the county seat of Jefferson County, and since 2003, the city's borders are coterminous with those of the county due to merger. Because it includes counties in Southern Indiana, the Louisville metropolitan area is regularly referred to as Kentuckiana. A resident of Louisville is referred to as a Louisvillian. Although situated in a Southern state, Louisville is influenced by both Midwestern and Southern culture, and is commonly referred to as either the northernmost Southern city or the southernmost Northern city in the United States.

Louisville has been the site of many important innovations through history. Notable residents have included inventor Thomas Edison, the first Jewish Supreme Court Justice Louis Brandeis, boxing legend Muhammad Ali, newscaster Diane Sawyer, writer Hunter S. Thompson, and actor Tom Cruise. Notable events occurring in the city include the first public viewing place of Edison's light bulb, the first library open to African Americans in the South, and medical advances including the first human hand transplant, the first self-contained artificial heart transplant, and the development site of the first cervical cancer vaccine.