Nathaniel Pope, a politician and jurist from the Illinois Territory and State of Illinois was the Pope County namesake.

Pope County was created on 10 December 1816 from Gallatin and Johnson Counties. The first permanent settlement in what became Pope County was the modern-day Golconda in 1798.

In 1926, a steam shovel of the United Gas Improvement company which was building a dam on the Ohio River below Golconda, uncovered a two feet long piece of ivory mammoth tusk. It is currently on display at the Pope County Historical Society Museum. Come see it!

In 1824, a vote was held on amending the constitution in Illinois to allow slavery. It was defeated by a margin of 1,638 votes. Pope County cast 273 votes for it and 124 against it. 

On 25 June 1816, Silvey, a 24 year-old Negro servant of John Morris was indentured to him for a period of 40 years for a payment of $400.00. This was the first of several such registrations entered int eh courthouse in Pope County.

The Cherokee Trail of Tears entered Illinois at Berry's Ferry in Golconda and passed along the trail James Lusk had earlier established past Allen Springs about a mile southwest of present day Dixon Springs.

The Church at Waltersburg, the Immanuel German M. E. Church, was the center of county Sunday School activities and held annual conventions for many years.

In 1887 Phil Craig and Sim V. Clanahan started the Enterprise and in 1889 purchased the Herald, consolidating the two papers into the Herald-Enterprise. The paper now owned by Sandra Cowsert is still publishing news of Pope County.

The Village of Hamletsburg in southern Pope was surveyed by J. E. V. Hanna in 1859. It was named for Hamlet Ferguson, an early civic leader and Illinois state legislator, who operated a ferry across the river to Kentucky in the region.

The community of Miller Grove east of Glendale was founded by freedman who came to Pope County in 1844. The Miller Grove Cemetery is believed to be the first all black cemetery in Illinois. Life in the community revolved around Mt. Gilead Methodist Church and school. The last family left the area in 1925 and archaeological excavations in recent years have been undertaken by Southern Illinois University. Oral histories passed down indicate families from the community were involved int he Underground Railroad.