Ripley County, Missouri was formed in 1831 from Wayne County, Missouri.
Located deep in the rugged, wooded hills of Southern Missouri, the area remained sparsely settled throughout the 19th century. Although organized in 1833, the county did not assume its present size until 1872.
When Congress created the Territory of Missouri in 1812, what became Ripley County was in New Madrid County. Three years later, Lawrence County was established, which included all of southern Missouri west of the St. Francis River and a portion of northern Arkansas. The seat of justice for Lawrence County was at Davidsonville in present-day Arkansas. In 1818 Wayne County was formed. This massive county included nearly one-fifth of the area in the Missouri Territory, with Greenville becoming the county seat.
In 1833 the General Assembly created Ripley County from part of Wayne County. The county then included present-day Ripley, Carter, Shannon, Oregon, and Howell Counties, with Van Buren as the county seat. Over the next 26 years, Ripley County's boundaries decreased as new counties were formed: Shannon (1841), Oregon, which included today's Oregon and Howell Counties (1845), and Carter (1859). The last boundary change took place in 1872.
Since most of the population lived in the south, voters moved the county seat to the new Doniphan, where a wooden courthouse was built. This building served the county until it was burned by Union troops, along with almost entire town of Doniphan, on September 19, 1864. William Russell, a county official, had earlier removed the county's record books and hid them in a cave south of town. They remained there until they were retrieved by the county clerk two years after the war.
Because of the chaos and destruction brought about by the Civil War, the courthouse was not replaced until 1871. A two-story brick courthouse was then built, using the $10,000 bond passed by the voters. It housed the administrative offices until it was destroyed by an accidental fire in January 1898.
Ripley County's current courthouse was designed by William F. Schrage of Kansas City, and was built by John McDonald Anderson of Emporia, Kansas in 1898–1899. A central tower, later destroyed during a 1929 tornado, dominated the two-story brick structure. Federal relief workers made repairs and renovations of the courthouse during the 1930s. An extensive remodeling project in the 1970s added central heating. The century-old courthouse is now listed on the National Register of Historic Places and celebrated its centennial during the 1999 Labor Day Homecoming Festivities.