DeKalb County was organized in February of 1845 and named after Baron De Kalb, a German-born member of the French army and a general in the American Revolution. The county is 270,720 acres of rolling prairie land in the northwest corner of Missouri, bordered by Clinton County on the south, Daviess County on the east, Gentry County on the north and Buchanan and Andrew counties on the west. There are nine different townships within the county, including Polk, Grant, Dallas, Sherman, Camden, Adams, Washington, Colfax and Grand River. There are also eight towns, including Maysville, Clarksdale, Amity, Union Star, Weatherby and major portions of Stewartsville, Osborn and Cameron.

DeKalb County is rich in history including the founding of Missouri's first Chautauqua in Maysville in 1896 by Thomas James T. Blair, Jr., who was inaugurated governor of Missouri in 1957. His father was also a Missouri Supreme Court Judge from 1915 to 1924.

The Old Council Bluffs Trace, a post road that went from Liberty, Missouri, to Fort Atkinson, Nebraska, ran through DeKalb County when it was opened in 1823 by the United States Army.

Maysville, the county seat, was the only town in the county until Stewartsville was founded in 1858. Stewartsville was founded, and much of the county's early economy was based upon the Hannibal-St. Joseph Railroad.

Osborn was laid out on the same railroad route in 1854. Twenty five years later in 1879, Union Star was established. Weatherby, Amity and Clarksdale were all founded in 1885 along The Chicago, Rock Island and Pacific Railroad route.

Three commissioners preside over the county. Today the county's economy thrives on the intersection of U.S. 36 and Interstate 35, in Cameron.