Due to warfare and exposure to infectious diseases after European contact, native tribes became depopulated.

In the eighteenth century, when the area was under Spanish rule, Native American peoples of Creek and other tribes migrated into present-day Florida from Georgia.

Glades County sponsors one of Florida's oldest recurring festivals.

Chalo Nitka Festival is a celebration of local history and culture, similar to a county fair.

The festival also draws attention to the long and friendly relationship between the local Seminole groups and Glades County settlers.

[8] As of the 2020 United States census, there were 12,126 people, 4,859 households, and 3,247 families residing in the county.

According to the Secretary of State's office, Republicans are a majority of registered voters in Glades County.

Florida Public Service Commission voted unanimously to deny a request by Florida Power and Light to build a huge coal-fired power plant in Glades County, that was to be located several miles to the west of Lake Okeechobee.

[24] The Glades County Commission also allowed the construction in 2007 of a 200-acre (0.81 km2) landfill on the southwest shore of Lake Okeechobee.