Around 1840, Fort DeSoto was established in present-day Hernando County in the northeast edge of present-day
Brooksville to protect settlers in the area from Native Americans. Fort DeSoto became a small community center, trading post, and way station on the route to
Tampa. When settlement by the fort began around 1845, it was alternatively known as Pierceville.
Then encompassing a significantly larger area of west central Florida than it does today, Hernando County was officially established on February 27, 1843, two years prior to Florida's admission into the Union. It was created from portions of Alachua, Hillsborough and Orange Counties and included all of present-day Citrus and Pasco Counties. Named for
Hernando de Soto,
 whose name has also been honored in
DeSoto County, Hernando County was briefly renamed Benton County in 1844 for
Missouri Senator Thomas Hart Benton, a strong supporter of territorial expansion who aided in the county's creation. However, Benton fell out of favor with the county's residents later in the decade due to his decision to support the
Missouri Compromise and the overall reversal of his stance on slavery, and the county's name reverted in 1850.
In December 1854, the legislature designated the small port town of
Bayport the county seat. Residents living in the eastern section of the county instead desired a more central place for the county government, and by 1855, voters had selected an inland site within five miles (8 km) of the center of the county at the town of Melendez. In 1856, the citizens of Hernando County chose to rename the town, their new County Seat,
Brooksville in honor of
South Carolina Representative Preston Brooks, who in the same year beat fierce abolitionist
Massachusetts Senator Charles Sumner with a cane in the Senate chambers, winning the Congressman great renown in the South.
In 1855, town founder Joseph Hale donated land for a county courthouse in the center of present-day Brooksville. Soon thereafter, the structure was completed.
Civil War, Hernando County primarily contributed foodstuffs, cotton, and lumber to the Confederacy. Although Union ships imposed a blockade on the port of
Bayport, runners enjoyed a great deal of success—enough to lead the Union in June 1864 to order some 150–250 troops to destroy Confederate stockpiles in the county. In early July, the expedition marched northward from Anclote River to
Brooksville, meeting some resistance from assembled Confederate troops hastily organized to protect the city. The Federal troops won this engagement (known locally as the Brooksville Raid
 and marched to Bayport, where they and an auxiliary force landing from gunboats sacked Rebel operations. The skirmish between Union raiders and local Confederates is reenacted annually in the county.
The county courthousewas destroyed by a fire on September 29, 1877. On June 2, 1887, the
Florida State Legislature divided Hernando County into three independent counties:
Pasco County to the south,
Citrus County to the north, and Hernando County in the middle. Since then, Hernando County's borders have remained unchanged.