The first settlement at Doniphan was made in the 1840s. The community was named for Alexander William Doniphan. A post office called Doniphan has been in operation since 1848.
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Early years
The earliest recorded permanent settlement in the area that would become Doniphan was that of Lemuel Kittrell in 1819. Kittrell built a grist and wood mill near his home that attracted additional settlers to the region. By 1841, the Kittrell settlement had grown to a sizeable village that included an inn, store, distillery, produce warehouse, tannery, justice of the peace and notary office, blacksmith, and a gunsmith.
The town of Doniphan was founded in 1847. Due to most of the population of Ripley County being concentrated in the southern half of the county, the county seat was moved from Van Buren to Doniphan the same year.
Civil War
Most residents of Southeast Missouri identified as southerners and sympathized with, or fought for, the Confederacy. During the winter of 1861–1862, the combination of harsh conditions and numerous skirmishes ruined crops and many families suffered. The residents of Doniphan were promised protection by Captain W. T. Leeper if they remained loyal to the Union, but the residents were mostly rebel sympathizers.
In 1862, Reverend Timothy Reeves, a Baptist minister in Doniphan, formed Reeves's Independent Company of Missouri Scouts, a militia group under the command of Confederate General John Sappington Marmaduke. On April 1, 1862, a skirmish lasting two days took place at the Doniphan Ford on Current River. Union forces were led by Captain Leeper, while pro-Confederate forces were led by Reverend Reeves. The skirmish resulted in many killed, wounded, or captured for both sides.
In 1863, Reeves combined his Independent Scouts with another militia group to form the 15th Missouri Cavalry Regiment, CSA.