Howell County is in southern Missouri. As of the 2020 census, the population was 39,750. The largest city and county seat is West Plains. The county was officially organized on March 2, 1851, and is named after Josiah Howell, a pioneer settler in the Howell Valley.

U.S. Route 63 is the portion of a north-south highway that runs through the U.S. state of Missouri from the Arkansas state line near Thayer to the Iowa state line near Lancaster.