By 1836, most of the present Downtown district had been incorporated into the City of Cleveland. Cleveland was founded in 1796 when Moses Cleveland landed on the east bank of the Cuyahoga River in the area now known as the "Flats". Cleveland remained a small village until 1827 when it became the northern terminus of the Ohio and Erie Canal. The opening of the canal and improvements to the harbor transformed the City into a commercial shipping port. The Flats became a wholesale district and the area at the top of the hill (now the Warehouse District) began to develop as the central business district and a residential area.

As the City grew, development continued to push eastward. During the 1870's and 1880's, the wholesaling district around the Flats moved up the hill into the Warehouse District. From the 1870's to the turn of the century, numerous mansions were built along Euclid Avenue, which became known as "Millionaires Row". Few of these buildings remain, as further commercial expansion hastened abandonment of Euclid as a residential street. Public Square, which was conceived in the "Original Plan for the Town and Village of Cleveland" in 1796 as an open space for a traditional New England town, received its first major improvement in the 1870's. It has subsequently gone through a series of major improvements in the 1890's, 1930's and 1980's.

In 1903, the Group Plan was adopted as a civic center plan to coordinate the construction of new buildings being planned by various levels of government. The plan was implemented with the development of the Federal Building (1910), County Courthouse (1911), City Hall (1916), Public Auditorium (1925), Library (1925), Board of Education Building (1930) and the Mall (1935). The Mall, Public Hall and Municipal Stadium (1931) were incorporated into the Great Lakes Exposition in 1936 and 1937, showcasing the strengths of the Great Lakes and attracting 7 million visitors.

Difficulties with the lakefront railroad depot during World War I resulted in the development of a new station on Public Square, planned and built by the Van Sweringen brothers. Excavation for the station began in 1924. The 52-story Terminal Tower was completed in 1927 and the train station opened in 1929. Terminal tower remained the tallest building in Cleveland until the Society Tower opened in 1991.

Air transportation was accommodated with the opening of Burke Lakefront Airport in 1947. The eastern boundary of Downtown was defined with the construction of the Innerbelt Freeway. The 3.25-mile stretch of highway was begun in 1954 and completed in 1962 and links I-71, I-77 and I-90 it services 100,000 vehicles daily.

Establishment and expansion of Cleveland State University and the redevelopment of Erieview Urban Renewal area had major impacts on Downtown in the 1960's and 1970's. During the 1980's and early 1990's, revitalization of Downtown continued with the renovation of the Playhouse Square theater district, redevelopment of the Flats for entertainment, renovation of the Terminal Tower complex into a mixed-use development, renovation of Warehouse District building for housing, development of North Coast Harbor for open space and museums and the development of the Gateway Sports Complex.