South Collinwood became part of the City of Cleveland when the villages of Collinwood and Nottingham were annexed to the City in 1910 and 1912, respectively. The area was first settled in 1812. Settlement increased with the establishment of numerous vineyards; and, by the 1870's, Collinwood had become the largest shipping point in the nation for grapes. By the 1890's, vineyards had been replaced by rail yards as the area's principal generator of economic activity.

Industrial development accelerated rapidly following construction of the Collinwood Rail Yards, a major switching center the Lake Shore and Michigan Southern Railroad. Residential development also expanded as many Italian immigrants moved to the South Collinwood area in the early 1900's.

In 1921, the Fisher Body Co. opened an automobile body plant at East 140th Street and Coit Road. By 1924 the plant employed 7,000 people and in 1926 Fisher Body became a division of General Motors. By World War II, the area around the Collinwood Rail Yards had become an international center for heavy manufacturing. During the war the plant made parts for tanks and employed 14,000 people. Land values in the Five Points area (the five-legged intersection of St. Clair, East 152nd and Ivanhoe) were the third highest in the City, exceeded only by those in Downtown and University Circle.

In the decades after World War II, the rise of freeways and the movement of heavy industry out of the nation's northeast and midwest regions resulted in the abandonment of many rail-oriented industrial properties in Collinwood. In the 1980's, the large Fisher Body plant was closed.

While the population of South Collinwood had gradually declined after its peak in 1930, since 1970 the decline has sharpened. In 1990 the population was approximately half African-American and half white. The population is segregated, however, with most African-Americans living west of East 152nd Street and most whites living east of East 152nd Street. Recent efforts to improve the Five Points retail district, and to make it a focal point of both communities, have included the construction of a new fire station and development of a new McDonalds.