According to archaeological studies, prehistoric people lived in this area as long ago as the Paleo-Indian period (before 6,000 B. C.).

However, archaeologists have made more extensive studies of those people known as the Mound Builders who lived here during the Caddoan Stage (A.D. 300 – 1200).

Early in the 19th century, Cherokee and Choctaw hunting parties made incursions that caused frequent conflict with the Osage.

The Missouri, Kansas and Texas Railway (also called MKT or Katy) built a line into Indian Territory, near the Three Forks.

The Arkansas, Verdigris and Grand rivers all converge in the county, causing that area to be called "Three Forks.

Donald Trump beat Hillary Clinton 62%-33% in 2016, which was a sharp right-turn from the competitive totals from Barack Obama's efforts in the prior two elections.

In February 2022, Republicans held a plurality of registered voters in Muskogee County for the first time in recent history.

Agricultural service industries consisted mainly of cotton gins, grain mills, and stockyards.

Cotton production declined dramatically during the Great Depression and was replaced by soybeans, wheat, feed grains, and grasses.

Truck farming became important during and after World War II, leading to the development of a canning and food-processing industry.

Sand and gravel pits, along with brick and glass manufacturing, developed and remained important employment sources.

O. W. Coburn built an optical business that became one of the largest in the nation and employed hundreds of workers.

State and federal employment has long been important, primarily in education and veterans' services.

[3] Education was a high priority after the Civil War, with schools started by churches, private individuals, and the Cherokee and Creek nations.

Higher educational opportunities were offered after 1880 when Bacone College, Oklahoma's oldest, began as Indian University in Tahlequah, but was moved to the Creek Nation in present Muskogee County in 1885.

Evangel Mission, a school at Union Agency for Creek freedmen, operated in the 1880s and now houses the Five Civilized Tribes Museum in Muskogee.