Holmes County is a county located in the U.S. state of Mississippi. As of the year 2000, the population was 21,609.
Its county seat is Lexington, Mississippi, which was named in honor of Lexington, Massachusetts. Like much of the state, Holmes County suffered during and after the Civil War.
Holmes County was the birthplace of the Order of the Eastern Star (a Masonic type lodge that offered membership to women.) Holmes County is also the birthplace of the 4-H movement, which began as a local community corn club.