When she returned to Chicago in 1910, Gaines began working at the Cook County Juvenile Court as a stenographer, which helped her become aware of the problems affecting the youth in her community. After World War I started, she found a new job with the US Department of Labor’s War Camp Community Service Program as an organizer for the girls’ division.
On October 7, 1914, McCoy married Harris Barrett Gaines, a law student at the time. They had two sons, Harris Barrett, Jr., in 1922 and Charles Ellis in 1924. Her children’s public school education offered a window into the desperate inequality of segregated schools.
In 1920, Gaines became the industrial secretary for the first African American branch of the YWCA in Chicago, and during the 1920s, she became involved with and took leadership positions in many different activist groups. Because of her association with groups such as the Chicago Urban League, Woman’s City Club, Woman’s Trade Union League, Illinois Women’s Voters’ League, the District Federation of Colored Women’s Clubs, University Society, and Household of Ruth, she quickly gained an excellent reputation in Chicago’s African American community for her extensive social work. Beginning in 1930, Gaines began working for the welfare department of Cook County, where she remained until 1945.
In 1939, Gaines founded the Chicago Council of Negro Organizations. She was president until 1953 and used her position to protest the inequality caused by segregated schooling. She secured improved facilities and established one of the first integrated nursery schools.
In 1940, Gaines became the first African American woman to run for the Illinois State Legislature. Although she lost that election, she became one of the organizers of the first March on Washington in 1941 and led 50 Chicago-area protesters to Washington, D.C., to meet with other demonstrators from across the nation. They formed committees that visited heads of government agencies to protest discrimination against blacks in employment. The National March on Washington Movement eventually resulted in President Franklin Roosevelt’s Executive Order 8802, which banned discrimination in companies that received federal funds.
She also championed the condition of women, and in 1947, she testified before the United Nations about discrimination and oppression of women of color in the US, becoming one of the first individuals in the world to address that issue before this international body.
In 1958, at the age of 66, Gaines received the George Washington Medal of Honor for her lifelong efforts in improving her community. The following year, she received the Fisk University Distinguished Alumni Service Award, and in 1962, Wilberforce University awarded her an honorary degree.
Irene McCoy Gaines died of cancer on April 7, 1964, in Chicago at the age of 72.