Greene County is located in the southwest part of the U.S. state of Missouri. As of the 2020 census, its population was 298,915. making it the fourth most-populous county in Missouri. Its county seat and most-populous city is Springfield. The county was organized in 1833 and is named after American Revolutionary War General Nathanael Greene…Greene County is located in the southwest part of the U.S. state of Missouri. As of the 2020 census, its population was 298,915. making it the fourth most-populous county in Missouri. Its county seat and most-populous city is Springfield. The county was organized in 1833 and is named after American Revolutionary War General Nathanael Greene. Greene County is included in the Springfield metropolitan area. It is in the area of the Ozark Mountains and foothills.