Cincinnati was founded in 1788 by John Cleves Symmes and Colonel Robert Patterson. Surveyor John Filson (also the author of The Adventures of Colonel Daniel Boon (cq) Daniel Boone) named it "Losantiville" from four terms, each of different language, meaning "The city opposite the mouth of the Licking River." "Ville" is French for "city," "anti" is Greek for "opposite," "os" is Latin for "mouth," and "L" was all that was included of "Licking River." In 1789 Fort Washington was built to protect the settlements in the Northwest Territory. The post was constructed under the direction of Gen. Josiah Harmar. The fort was named in honor of President George Washington.

In 1790, Arthur St. Clair, the governor of the Northwest Territory, changed the name of the settlement to "Cincinnati" in honor of the Society of the Cincinnati, of which he was president. The society honored General George Washington, who was considered a latter day Cincinnatus—the Roman general who saved his city, then retired from power to his farm. To this day, Cincinnati in particular, and Ohio in general, are home to a disproportionately large number of descendants of Revolutionary War soldiers who were granted lands in the state.

In 1802, Cincinnati was chartered as a village, and in 1819, it was incorporated as a city. The introduction of steam navigation on the Ohio River in 1811 and the completion of the Miami and Erie Canal helped the city grow to 115,000 citizens by 1850. The nickname Porkopolis was coined around 1835, when Cincinnati was the country's chief hog packing center, and herds of pigs traveled the streets. Called the "Queen of the West" by Henry Wadsworth Longfellow (although this nickname was first used by a local newspaper in 1819), Cincinnati was an important stop on the Underground Railroad, which helped slaves escape from the South. Cincinnati is also known as the "City of Seven Hills." The seven hills are fully described in the June, 1853 edition of the West American Review, "Article III -- Cincinnati: Its Relations to the West and South." The hills form a crescent from the east bank of the Ohio River to the west bank: Mount Adams, Walnut Hills, Mount Auburn, Vine-street Hill, Fairmont, Mount Harrison and College Hill.

Cincinnati was the site of many historical beginnings. It was the first city in the United States to establish a Jewish Hospital in 1850. It is where America's first municipal fire department was established in 1853. Established in 1867, the Cincinnati Red Stockings (later, the Cincinnati Reds) became the world's first professional (all paid, no amateurs) baseball team in 1869. In 1935, major league baseball's first night game was played at Crosley Field. Cincinnati was the first to build and own a major railroad in 1880. In 1902, the world's first reinforced concrete skyscraper was built, the Ingalls Building. "The Sons of Daniel Boone", a forerunner to the Boy Scouts of America, began in Cincinnati in 1905. Because of the city's rich German heritage, the pre-prohibition era allowed Cincinnati to become a national forerunner in the brewing industry. During experimentation for 6 years (until 1939), Cincinnati's AM radio station, WLW was the first to broadcast at an astounding 500,000 watts. In 1943, King Records (and its subsidiary, Queen Records) was founded, and went on to record early music by artists who became highly successful and influential in Country, R&B, and Rock. WCET-TV was the first licensed public television station, established in 1954. Cincinnati is home to WEBN, the longest running album oriented rock station in the United States, first airing in 1967. In 1976, the Cincinnati Stock Exchange became the nation's first all-electronic trading market.

As a pioneer-era city, it compared with Pittsburgh and Nashville. As a "Riverboat" and canal-era city, it compared with Louisville, St. Louis and New Orleans. As an immigrant, industrial city it compared with Brooklyn, Philadelphia, Cleveland, Chicago, and Detroit.

Because of its river setting and extensive park system, many commentators have remarked on Cincinnati's beauty, including Winston Churchill, who called it "the most beautiful of America's inland cities." The city's picturesque skyline was used as a backdrop for the fictional city of Monticello on the soap opera The Edge of Night, one of the many soap operas sponsored by Cincinnati soap maker Procter & Gamble. In fact, Procter & Gamble created the genre of the "soap opera" when it helped launch the Ma Perkins radio program in 1933.

In August 1966, Cincinnati rock music fans had the privilege of seeing The Beatles perform at a large outdoor venue at Crosley Field. This was during the British group's final concert tour of the United States and Canada.

Tragedy struck the Cincinnati metropolitan area on May 28, 1977, when a suburban nightclub burned, taking the lives of 165 persons. The Beverly Hills Supper Club fire remains the third deadliest fire at a nightclub in American history.

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