Durham passed the bar in 1926 and established his practice in Sherman, Texas and began his long career in civil rights by taking on civil rights cases.  His office was burned in the Sherman riot of 1930 when the lynch mob burned the black business district.  Because Durham had a lucrative practice service as lawyer for an insurance company, he was able to spent time fighting for civil rights.
During World War II, William Durham moved from Sherman to Dallas in 1943 because of gasoline shortages and his growing involvement with the NAACP.  There he achieved prominence as a civil rights champion and leader for the NAACP as well as his reputation in the court system.  He took part in 40 cases involving school integration, voting rights, and equalization of teachers' salaries.  

Durham with Thurgood Marshall in 1950

In the late 1940s William J. Durham was counsel for Herman M. Sweatt, a postal employee and political activist who as a result of his past experiences wanted to attend law school.  There being no law school in Texas for African-Americans, he applied for admission to the University of Texas law school upon Durham's advise.  Upon denial of his admission by University of Texas President, Sweatt filed a law suit against the college President in 1946.  In 1950 Sweatt and Durham won the case based on the fact that an equal law education in the state of Texas was not offered to African Americans and thus University of Texas was required to admit African American applicants.