The St. Clair-Superior neighborhood began to urbanize in the 1870's and 1880's, following the area's annexation to the City of Cleveland. Industries located north of St. Clair Avenue (in the present Lakeside Industrial District) attracted Slovenian and Lithuanian immigrants in addition to smaller numbers of Croatians, Germans and Poles.

The Slovenian and Lithuanian communities settled along St. Clair and Superior Avenues respectively. St. Vitus Roman Catholic Church has been the center of religious life for Cleveland's Slovenian community since its establishment in 1894 at East 61st and Glass. The landmark Slovenian National Home, with a 1,000-seat social hall, was built at East 64th and St. Clair in 1924. Members of the Lithuanian community founded the Lithuanian Building and Loan Association in 1906 and built the present St. George Lithuanian Church at East 40th and St. Clair in 1921.

Population in the St. Clair-Superior neighborhood peaked at over 38,000 in 1920 and then declining gradually until the 1970's when the loss accelerated. The number of residents fall from approximately 22,000 in 1970 to under 15,000 in 1980 and to around 12,000 in 1990. During that time period, the neighborhood also lost one-third of its housing units. Despite this loss, property conditions remain generally good on many blocks, which are characterized by well-manicured front lawns and urban gardens. Although the local Eastern European community was bolstered by a second wave of immigration following World War II, the neighborhood has become more heterogeneous in recent decades. African-American residents now comprise over half of St. Clair-Superior's population

Recent developments in the neighborhood include the renovation of the closed Hodge School at East 74th and Korman for a mixed-use development and a $2 million improvement projects at Gordon Park, which included the construction of five lighted ball diamonds.