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Douglas County, Kansas has a rich and diverse history dating back to the time of Native American settlements. The Kaw (or Kanza) people were the original inhabitants of the area before European settlers arrived in the 19th century. The county takes its name after Stephen A. Douglas, a prominent 19th-century politician.

In the mid-1800s, Douglas County played a crucial role in the "Bleeding Kansas" era, a period of conflict over whether Kansas would be a free or slave state. Lawrence, the county seat, was a stronghold for anti-slavery activists and had a significant impact on the national debate on slavery. The infamous Lawrence Massacre in 1856, where pro-slavery forces attacked the town, further intensified the tensions.

During the Civil War, Douglas County continued to be a center for abolitionist activities. The county's residents played vital roles in supporting the Union army and providing aid to escaped slaves traveling the Underground Railroad. The historic Eldridge Hotel in Lawrence served as a temporary headquarters for several Union generals.

In the post-war years, Douglas County experienced significant growth and development. The University of Kansas was established in Lawrence in 1866, becoming a major educational and cultural institution for the county and the region. As the county grew, agriculture played a vital role in its economy, with thriving wheat and dairy industries. Today, Douglas County continues to preserve its historical significance while embracing modern advancements and maintaining a strong sense of community.