The county was an important lead and zinc mining region during the early 1900s, and in 1983 the Tar Creek Superfund site was inaugurated to clean up tailings and prevent groundwater and waterway contamination with leachates.

Archaeological studies indicate this area was inhabited for thousands of years by succeeding cultures of prehistoric indigenous peoples.

[3] The Osage Nation had moved into the area from Missouri and Kansas by the 19th century, under pressure from European-American encroachment on their lands.

In 1831, the Federal Government reacquired part of what would eventually become Ottawa County in order to forcibly relocate several other tribal nations that had been systematically displaced from the Midwest under its Indian Removal program.

This county is part of the Tri-State district, a center of lead and zinc mining through the first half of the 20th century.

In 1996 the government found that 34% of the children of Picher had lead poisoning due to groundwater, air and dust effects.

Environmental remediation was conducted, but the state and federal government have since closed Picher as a city and relocated nearly all its residents since the early 21st century.

It has since become a Republican stronghold similar to the rest of the state, with Donald Trump's 2024 53 point win over Kamala Harris being the most lopsided margin of victory in the county's electoral history.

[3] In 1926, at the region's peak of production, Ottawa County was the largest source of lead and zinc in the world.

Such areas have been designated as part of the Tar Creek Superfund Site by the US Environmental Protection Agency.

Said counties combined are the third-largest tourism destination in the state, following only the Oklahoma City and Tulsa metropolitan areas.