On the north bank of the Missouri River, Howard County was settled primarily by migrants from the Upper Southern states of Kentucky, Tennessee and Virginia. They brought slaves and slaveholding traditions with them, and quickly started cultivating crops similar to those in Middle Tennessee and Kentucky: hemp and tobacco. Howard was one of several counties settled mostly by Southerners along the Missouri River in the central part of the state. Given their culture and traditions, this area became known as Little Dixie and Howard County was at its heart. In 1860 slaves made up 25 percent or more of the county's population. Residents generally supported the Confederacy during the Civil War. After the Civil War, Howard County was a dangerous place for African Americans. The county witnessed five lynchings between 1891 and 1914. The victims—Olli Truxton, Frank Embree, Thomas Hayden, Arthur McNeal, and Dallas Shields—were all African American men.
According to the U.S. Census Bureau, the county has a total area of 472 square miles (1,220 km2), of which 464 square miles (1,200 km2) is land and 7.7 square miles (20 km2) (1.6%) is water.
There were 3,836 households out of which 31.50% had children under the age of 18 living with them, 55.30% were married couples living together, 9.50% had a female householder with no husband present, and 31.40% were non-families. 27.30% of all households were made up of individuals and 13.30% had someone living alone who was 65 years of age or older. The average household size was 2.46 and the average family size was 2.98.
In the county the population was spread out with 24.00% under the age of 18, 13.30% from 18 to 24, 25.20% from 25 to 44, 21.30% from 45 to 64, and 16.10% who were 65 years of age or older. The median age was 37 years. For every 100 females there were 94.00 males. For every 100 females age 18 and over, there were 94.40 males.
The median income for a household in the county was $31,614, and the median income for a family was $40,167. Males had a median income of $26,369 versus $19,950 for females. The per capita income for the county was $15,198. About 7.50% of families and 11.60% of the population were below the poverty line, including 14.70% of those under age 18 and 14.40% of those age 65 or over.