Judge Williams, a pioneering African-American jurist, began her career as a teacher in inner-city Detroit. After earning her law degree from Notre Dame University in 1975 she began her legal career as a law clerk in the United States Court of Appeals for the Seventh Circuit. From 1976 to 1985 Williams worked as an Assistant U.S. Attorney in Chicago. In 1985 Williams was the first African-American woman appointed U.S. District Court Judge for the Northern District of Illinois and became one of the youngest persons ever appointed to an Article III federal judgeship. In 1999 Williams became the first African American appointed to the United States Court of Appeals for the Seventh Circuit and the third African-American woman to serve on any federal appeals court. From 1993 to 1997 Williams also served as chair of the Court Administration and Case Management Committee of the United States Judicial Conference. Since 1999 she has served as president of the Federal Judges Association.

In 1977 Williams co-founded Minority Legal Education Resources to help teach minority and other lawyers how to pass the Illinois bar. In 1993 she co-founded Just the Beginning Foundation, dedicated to celebrating the contributions of African-American federal judges.