In the winter of 1935, four graduates of Lincoln University--a traditionally black school about 30 miles away in Jefferson City, Missouri--were denied admission to UMC's graduate school. One of the students, Lloyd L. Gaines, brought his case to the United States Supreme Court. On December 12, 1938, in a landmark 6-2 decision, the court ordered the state of Missouri to admit Gaines to UMC's law school or provide a facility of equal stature. Gaines, however, disappeared in Chicago on March 19, 1939.

Although Gaines did not survive to benefit from the decision, the case led directly to the 1954 case of Brown v. Board of Education, which declared segregation in education unconstitutional. The UM Board of Curators renamed the school's Black Culture Center in Gaines' honor in 2001.

Undergraduate divisions were integrated by court order in 1950, when the university was compelled to admit African Americans to courses that were not offered at Lincoln University.