[8] 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.

[10] 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.

[11] 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.

[12] On April 1, 1862, a skirmish lasting two days took place at the Doniphan Ford on Current River.

[13] In 1863, Reeves combined his Independent Scouts with another militia group to form the 15th Missouri Cavalry Regiment, CSA.

In 1864, Union troops entered Doniphan and burned most of the town, including the wooden courthouse.

[15] According to the United States Census Bureau, the city has a total area of 1.38 square miles (3.57 km2), all land.

Climate is characterized by relatively high temperatures and evenly distributed precipitation throughout the year.