Butler County is a county located in the southeast Ozark Foothills Region in the U.S. state of Missouri. As of the 2020 Census, the county's population was 42,130. The largest city and county seat is Poplar Bluff. The county was officially organized from Wayne County on February 27, 1849, and is named after former U.S. Representative William O. Butler, who was also an unsuccessful candidate for Vice President of the United States.