The state of Virginia rewarded General George Rogers Clark and his regiment for their victorious capture of Forts Kaskaskia, Cahokia, and Vincennes from the British, by granting them 150,000 acres (610 km2) of land.

A small portion of this land, 1,000 acres (4.0 km2), became known as Clarksville, the first authorized American settlement in the Northwest Territory, founded the next year in 1784.

This original area in Clark County was subsequently altered and reduced with the formation of other counties: Harrison (1808), Franklin, Jefferson, and Wayne (1811), Switzerland and Washington (1814), Jackson and Ripley (1816), Jennings (1817), Crawford and Randolph (1818), Fayette and Floyd (1819), Scott (1820), Union (1821), Decatur and Rush (1822).

[3] Jeffersonville was platted in 1802, and on June 9 the Territorial Governor (William Henry Harrison) ordered that it be regarded as the county seat.

Many settlers were Quakers who had migrated from North Carolina to escape the oppressive conditions of the slave states and did not want to see slavery be established in Indiana.

[5] From its beginning Clark County's history, culture and growth have been linked to the development of the river.

Early nineteenth-century steamboats transported goods to the upper Ohio, providing opportunities for commercial and industrial growth in the county.

Later Howard shipyards reorganized as Jeffersonville Boat and Machine Company (Jeffboat) — a current major employer (1991).

[6] When the war ended, the county experienced significant residential and commercial growth, aided by the 1956 Interstate Act.

Clark County has diversified its economic base, lessened its dependency on the river, and continues to develop in new directions.

[7] The highest point on the terrain is a ridge WNW of Henryville near the border with Scott County, at 1,030 ft (310 m) ASL.

[12] Two towns in Clark County, Marysville and Henryville suffered major damage during the tornado outbreak of March 2–3, 2012.

Since the start of the second millennium, the county has trended strongly Republican, moving away from its previous near-bellwether status.

The commissioners are charged with executing the acts legislated by the council, collecting revenue, and managing the day-to-day functions of the county government.

City and Town Courts have jurisdiction to hear Ordinance violations and misdemeanor prosecutions, as well as civil actions where the amount in controversy does not exceed five hundred dollars ($500).

The Circuit and Superior Court Judges are elected on a partisan basis, must reside within the county, and serve six-year terms.

The City and Town Court Judges are elected to four-year terms on a partisan basis, and must reside within the City/Town.

[15] Clark County is part of Indiana's 9th congressional district and is represented in Congress by Republican Trey Hollingsworth.