Middletown is a city in Butler and Warren counties in the southwest of the U.S. state of Ohio. The population at the 2020 census was 50,987. It …Middletown is a city in Butler and Warren counties in the southwest of the U.S. state of Ohio. The population at the 2020 census was 50,987. It is part of the Cincinnati metropolitan area, 29 miles northeast of Cincinnati and 20 miles southwest of Dayton.