In 1841, Jasper County, Missouri, was formed from Greene County and in 1842, Carthage was laid out as the county seat with a public square surrounding a simple frame courthouse. By the next decade, a brick building for the county government was constructed and stood until destroyed by years of guerilla warfare during the Civil War. Today, the Battle of Carthage is memorialized with the Civil War Museum and the separate Battle of Carthage State Historic Site.  This 7.4-acre tract is the site of the final confrontation of a 12-hour running battle, which began nine miles north of town on the morning of July 5, 1861. Missouri's Gov. Claiborne Fox Jackson commanded the 6,000 Southerners that forced Col. Franz Sigel and his 1,000 Union men to retreat down the stagecoach road to Sarcoxie. An interpretive shelter with displays explains the history of the battle, and the site remains just as it was when the victorious Southern troops camped there on that summer evening after the battle.

Like that 1854 brick courthouse, the thriving town of Carthage was destroyed by war, too. When new and former inhabitants returned in late 1865 and 1866, all they found was "a haunt for wolves and owls" as future judge and biographer Malcolm McGregor recalled. But soon the town reclaimed her position as the agricultural and social hub of southwest Missouri. Carthage also began to attract more industrial concerns and laid her economic foundation that still exists today in a very diverse business and industrial economy.

By the mid-1880s, Carthage had a foundry, furniture factory, two woolen mills, 4 grain mills, a pottery, a brick manufacturer, a plow works and numerous liveries, agricultural implement dealers and regional wholesalers of clothing, groceries and hardware goods. But by the late 1880's Carthage discovered her greatest wealth lay underneath her in deposits of limestone, lead and zinc. The stone quarries were on the edges of town while many of the mines were developed within a few miles from her borders. Through these gifts from the earth, Carthage soon became one of the most prosperous towns in the state and became known as the Queen City of the South West in the 1890s.

Other industries grew to supply products to the town's growing number of residents as well as to markets throughout the four-state area and beyond. By 1900, Carthage had approximately 12,000 inhabitants and over one hundred business and industrial concerns.