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 (D-Kentucky), who was also an unsuccessful candidate for Vice President of the United States. The first meeting in the Butler County Courthouse was held on June 18, 1849.

Poplar Bluff is a city in Butler County in southeastern Missouri, United States. It is the county seat of Butler County and is known as "The Gateway to the Ozarks" among other names. The population was 16,225 at the 2020 census. The Poplar Bluff Micropolitan Statistical Area consists of all of Butler County. The city is at the crossroads of U.S. Route 60 and U.S. Route 67.