The land comprising Dunklin County was previously inhabited by the Delaware Tribe of Indians, who had lived in the area since the early 1800s.

The first courthouse, a two story log cabin, in the county was erected in 1847 by Hiram Langdon in Kennett.

The most predominant denominations among residents in Dunklin County who adhere to a religion are Southern Baptists (64.11%), Methodists (8.66%), and Churches of Christ (6.74%).

It is located one nautical mile (1.85 km) southeast of the central business district of Kennett, which owns the airport.

[19] The county no longer has a hospital as the Twin Rivers Regional Medical Center closed on June 11, 2018.

Dunklin County, Missouri is placed in the Paducah, KY, Cape Girardeau, MO, & Harrisburg, Illinois Television Market.

Claire McCaskill was reelected to her second term in 2012 with 54.81 percent of the statewide vote over former Republican U.S. Representative W. Todd Akin of Town & Country and Libertarian Jonathan Dine of Riverside; Dunklin County gave McCaskill just over 50 and a half percent of the vote.

Roy Blunt was elected to his first term in 2010 with 54.23 percent of the statewide vote over former Democratic Missouri Secretary of State Robin Carnahan, Libertarian Jonathan Dine of Riverside, and Constitutionalist Jerry Beck of Novelty; Dunklin County voters backed Blunt with just under 62 and a half percent of the vote.

Smith won a special election on Tuesday, June 4, 2013, to complete the remaining term of former Republican U.S. Representative Jo Ann Emerson of Cape Girardeau.

Like most rural areas throughout Missouri, voters in Dunklin County generally adhere to socially and culturally conservative principles but are more moderate or populist on economic issues, typical of the Dixiecrat philosophy.

The proposition strongly passed every single county in Missouri with 78.99 percent voting in favor as the minimum wage was increased to $6.50 an hour in the state.

In the 2008 Missouri Presidential Preference Primary, voters in Dunklin County from both political parties supported candidates who finished in second place in the state at large and nationally.

Senator Hillary Clinton (D-New York) received more votes in Dunklin County, 2,587, than any candidate from either party during the 2008 Missouri Democratic presidential preference primary.

The 2,587 is more votes than the total number cast in the entire Republican primary in Dunklin County.