Kentuckians played a large role in the NAACP. William English Walling  from Louisville, Kentucky (1877–1936), an American labor reformer and socialist educated at the University of Chicago, the Hull House and Harvard Law School, brought his interest in women's rights to his work with the American Federation of Labor and founded the National Women's Trade Union League. A few years later, the Springfield Race Riot of 1908 in Illinois informed his work with Mary White Ovington and Henry Moskowitzto form the NAACP.

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The Kentucky branch of the NAACP gained national recognition as early as 1940 in Louisville, Kentucky. The NAACP had already supported several court cases to protest the unequal pay of African Americans teachers. Vallateen Virginia Dudley Abbington (1907–2003), one of several school teachers in Louisville who petitioned against the differential in pay, became a plaintiff in a NAACP suit argued by Thurgood Marshall that led to the removal of a 15 percent salary discrepancy between black and white teachers in the Louisville public schools. The case, Abbington v Board of Education of Louisville (KY), filed on December 5, 1940, caused the School board to agree to equal pay, but only if Mrs. Abbington from Jackson Junior High School dropped the lawsuit. The lawsuit was dropped and the salaries of teachers in Louisville no longer differed on the basis of race.

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The Kentucky branch of the NAACP also fought against other discrimination through the civil rights movement  and beyond. In the case of Eilers v. Eilers, attorney James Crumlin, Sr. of the NAACP Legal Defense and Education Fund, helped Anna sue for custody of her five children from her ex-husband, George Eilers of Jefferson County, Kentucky.  In 1964 Eilers had successfully sued his former wife (a white woman from New Haven, Kentucky.) after she married Marshall C. Anderson, an African American man, gaining custody of their children since interracial marriage was illegal in Kentucky at the time. Another important leadership role of the NAACP in Kentucky was in the 1970s when the NAACP of Louisville and the Kentucky Civil Liberties Union worked together to fight segregation in the Jefferson County Public Schools.