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Charles Mix County is located in the southeastern part of South Dakota, and it has a rich history dating back to the 18th century. The region was originally inhabited by Native American tribes, including the Yankton Sioux and the Arikara. European settlement began in the mid-19th century, with fur traders and missionaries establishing contact with the native tribes. The county was officially established in 1862 and named after an early settler, Charles Eli Mix.

During the late 19th century, Charles Mix County experienced rapid growth and development. The arrival of the railroad in the 1870s brought new opportunities for trade and commerce, leading to the establishment of towns such as Lake Andes, Wagner, and Platte. Agriculture became the county's primary industry, with farmers cultivating crops like wheat, corn, and oats. The county's fertile soil and proximity to the Missouri River also attracted ranchers, who built large livestock operations.

The early 20th century saw further advancements in agriculture and infrastructure in Charles Mix County. The introduction of mechanized farming equipment, irrigation systems, and improved transportation networks helped boost agricultural productivity and expand the county's economy. As a result, the population grew steadily.

Like many rural areas, Charles Mix County faced challenges during the Great Depression of the 1930s. Many farmers struggled with drought and low crop prices, leading to economic hardships. However, the county rebounded with the help of federal programs and the resilience of its agricultural community.

In recent decades, Charles Mix County has continued to evolve. While agriculture remains the backbone of its economy, the county has also embraced diversification in other sectors, such as tourism and manufacturing. Today, Charles Mix County is known for its beautiful landscapes, including the scenic Missouri River, as well as its welcoming communities and strong sense of heritage.