In the southwest corner of the state and at the northern edge of the Ozark highlands, Springfield, known as Ozark Mountain Country's Big City, is near some of Missouri's most picturesque scenery and recreational areas. A few settlers came here as early as 1821, but settlement was temporarily discouraged when the government made southwestern Missouri a reservation. Later, the tribes were moved west and the town began to develop. Its strategic location made it a military objective in the Civil War. The Confederates took the town in the Battle of Wilson's Creek, August 10, 1861; Union forces recaptured it in 1862. Confederate attempts to regain it were numerous but unsuccessful. "Wild Bill" Hickock, later one of the famous frontier marshals, was a scout and spy for Union forces headquartered in Springfield.

Springfield's growth has been largely due to a healthy economy based on diversified industry; manufacturing and the service industry provide the majority of jobs. Springfield is the home of six major colleges and universities, including Southwest Missouri State University.