Established in September 1843, Murphysboro is the second county seat of Jackson County. Its founding is tied to the disastrous fire that destroyed the courthouse in first county seat in Brownsville. The fire proved to be the catalyst to move the county seat to a more central location. The name was decided when William C. Murphy’s name was drawn from a hat containing the names of the three commissioners who chose the new location. The 20-acre tract of land which comprised the boundaries of Murphysboro was donated by Dr. John Logan and Elizabeth Logan. Logan County, Illinois is named after Dr. Logan.

The son of the site's donors, Major General John A. Logan was a famous figure in the late 19th century. At the outbreak of the Civil War he was a U.S. Congressman. He would resign his commission and return to Illinois where he entered the Union Army as Colonel of the 31st Illinois Volunteers, a unit that he organized. Logan would rise to the rank of Major General and was in command of the Army of the Tennessee. After the war he reentered politics and was reelected to the House of Representatives and to the U.S. Senate. In 1884 he ran as the Vice Presidential candidate on the unsuccessful Republican ticket with James G. Blaine. Logan was also the leader of the Grand Army of the Republic, an organization for Northern Civil War veterans, and in this capacity he issued a proclamation in 1868 that "Decoration Day" should be observed nationwide. It was observed for the first time on May 30 of the same year. The date was chosen because it was not the anniversary of a battle and would ultimately become known as Memorial Day. The General John A. Logan Museum is located in Murphysboro and interprets Logan’s life as well as 19th century life in Southern Illinois.

Murphysboro lies within the Shawnee National Forest and there are many opportunities for nature lovers to take advantage of. These include Murphysboro Lake State Park, Lake Kincaid, Cedar Lake, LaRue Pine Hills, and the Shawnee Hills Wine Trail.