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Ohio's county seat, Cincinnati is a major metropolis in the state. The city was founded in 1788 on the northern bank of the Ohio River, which forms the boundary between Ohio and Kentucky. Economically and culturally, the city dominates the greater Cincinnati region. Cincinnati is the third-largest city in Ohio and the 64th-largest city in the United States, with a population of 309,317 (the metropolitan area has an estimated population of 2,256,884). From 1840 to 1860, it was the sixth-most populated city in the United States, and it remained in the top 10 most populous cities in the country throughout the most of the 19th century, trailing behind only New Orleans and the older, established colonies of the United States eastern shore.

When compared to East Coast towns of the same era, Cincinnati, a rivertown crossroads at the juncture of the North, South, East, and West, evolved with fewer immigrants and less influence from Europe. However, many of the city's cultural institutions were established by German-speaking immigrants. Changes in trade patterns and the declining importance of freight transportation brought about by the rise of railways over steamboats slowed Cincinnati's development significantly by the end of the nineteenth century. St. Louis, which for decades following the Civil War served as the gateway to westward migration, and Chicago, which expanded on the backs of strong commodities exploitation, economics, and the railways, both overtook the city in population.

There are four professional sports teams based in Cincinnati: the Cincinnati Reds of MLB, the Cincinnati Bengals of NFL, FC Cincinnati of MLS, and the Cincinnati Cyclones of the minor league ice hockey. The University of Cincinnati, originally established in 1819 as a municipal college, has grown to become one of the fifty biggest universities in the United States. Many buildings in downtown Cincinnati date back 200 years or more and yet seem as good as new. During the late 19th and early 20th centuries, Cincinnati had a period of national prominence as the "Paris of America," a moniker earned in large part by the city's grand architectural achievements, including the Music Hall, Cincinnatian Hotel, and Shillito Department Store. William Howard Taft, the 27th President of the United States and a former Chief Justice, was born in Cincinnati.