[4] In the mid to late 18th century, a group of Native Americans from Chiaha chiefdom settled in what is now Jefferson County.

It was named for Thomas Jefferson, third president of the United States, who had died the year before the county's establishment.

[6] In the two decades leading up to the American Civil War, cotton was the primary source of income in the county, with about seventeen percent of all Florida cotton being grown in Jefferson County.

Following emancipation, the black population of Jefferson County continued to grow.

To serve the relatively large black population in the county, the Freedmen's Bureau established an office in Monticello sometime around early 1866.

The 2020 United States census counted 14,510 people, 5,816 households, and 3,762 families in Jefferson County, Florida.

30.2% of households consisted of individuals and 15.4% had someone living alone who was 65 years of age or older.

[19] The 2016-2020 5-year American Community Survey estimates show that the median household income was $49,081 (with a margin of error of +/- $7,142).

28.1% of all households were made up of individuals, and 10.6% had someone living alone who was 65 years of age or older.

From 2000 to 2012, while Democratic candidates for President won the county, the margin dwindled over time; in 2016, the county voted for Donald Trump, the first time that it had voted for a Republican presidential candidate since 1988.

Private Aucilla Christian Academy enrolls about half as many students as the Jefferson County public schools.

It is located in the building that once housed the old Jefferson High School library.