Originally a part of Brooklyn Township, Ohio City was incorporated as a municipality on March 3, 1836, just two days before the incorporation of the "rival" City of Cleveland. It was annexed to Cleveland in 1854. The area's location near the mouth of the Cuyahoga River attracted settlers from New England and, later, from Ireland and Germany, seeking jobs at the docks, mills, foundries, distilleries and bottling works.

"Whiskey Island" (site of an 1830's whiskey distillery), "The Angle" (north of Detroit Avenue and east of West 28th Street) and "Irishtown Bend" (south of Detroit Avenue and east of West 25th Street) became early settlements of the Irish immigrants, many of whom occupied hastily-erected tarpaper shacks.

Housing in Ohio City dates principally from the late 19th century. The predominantly Victorian-style one- and two-family buildings range from modest working class houses to the luxurious residences on portions of Franklin Boulevard and Clinton Avenue. The commercial district at Lorain and West 25th was first established in 1840 as "Market Square". The Pearl Street Market, a one-story wooden building built in 1868, was replaced by the present West Side Market, which was built in 1912.

Ohio City's population climbed from just over 4,000 in 1850 to 33,000 in 1910. During the following six decades, the neighborhood's population declined gradually to 20,000 in 1970 and then -- following a citywide trend (and due to the construction of I-71 and I-90) -- fell sharply to under 13,500 in 1980. Also during the 1970's, the neighborhood's population began to diversity as the proportion of non-white residents rose from 7% to 30%. The proportion of Hispanic residents rose to nearly 19% by 1980 and to over 25% in 1990.

Countering this population loss, however, has been the rediscovery of the area's historic architecture and slow but steady residential and commercial restoration activity, including rehabilitation of the landmark West Side Market. Construction of the Market Plaza shopping center and the Franklin Green townhouses, as well as development of the Nautica entertainment complex on the west bank of The Flats, has also added new vitality to the neighborhood.