Hernando County is located on the central west coast of Florida (the Sun Coast), north of Tampa Bay. Officially created on February 24, 1843 and named after Spanish explorer Hernando de Soto, Hernando County now contains 478 square miles of land area and 111 square miles of water surface. The county seat is Brooksville.

Fort DeSoto was built around 1840 to protect local settlers from raids by the Seminole. The Fort, near the eastern edge of present-day Brooksville, became a trading post and community center for the settlers who began flowing into the area around 1845. The small town of Bayport was the original county seat but many settlers on the east side of the county wanted a county seat more in the center of the county. A site was chosen in what was then known as Melendez and voters made that the county seat. In 1856, the name of Melendez was changed to Brooksville (in honor of South Carolina Representative Preston Brooks, famous for caning abolitionist Senator Charles Sumner of Massachusetts in the Senate chambers).

During the Civil War, Hernando County contributed a lot of cotton, lumber and food to the Confederacy through the services of a number of successful blockade-runners based in Bayport. In June, 1864, 150-250 Union troops marched north from the Anclote River area to Brooksville to destroy any stockpiles of materials they came across. This is now known as the "Brooksville Raid," and is re-enacted every year in January at the Sand Hill Scout Reservation. The Union troops won the engagement at Brooksville and, after completing their mission there, marched to Bayport and sacked the town.

Part of the Chassahowitzka National Wildlife Refuge is in Hernando County. Interstate 75 crosses Hernando County (north/south) on the east side of the county. The western part of the county is served by State Road 41, the Suncoast Parkway (a designated scenic highway and toll road) and by US Highway 19.