In the early 19th century, Lauderdale, who moved to West Tennessee, became a major in General John Coffee's cavalry of volunteers.

Later promoted to lieutenant colonel, he commanded a brigade of mounted riflemen, serving under Andrew Jackson.

This area was once claimed by both the Chickasaws and Cherokees, necessitating a cession of territory from each tribe before the settlement could be established.

Rogersville, lying some 23 miles (37 km) to the east of Florence, was named for John Rogers, an Indian trader, whose sons were fast friends of the great Sam Houston.

The town of St. Florian was established in 1872 on the Jackson Highway and named by its Catholic founders (of German descent) for their patron saint.

[6] The county's entire southern and western boundaries are dictated by the Tennessee River, essentially forming a wedge between the river and the state of Tennessee that even extends past the remainder of the border between Alabama and Mississippi.

As of the 2020 United States census, there were 93,564 people, 38,761 households, and 23,883 families residing in the county.

According to the 2000 census,[16] the largest ancestry groups in Lauderdale County were English 41.9%, African 13.85%, Scots-Irish 9.66%, Scottish 4.11%, Irish 3.19% and Welsh 2.5% In 2000, there were 36,088 households, of which 30.40% had children under the age of 18 living with them, 55.80% were married couples living together, 10.80% had a female householder with no husband present, and 30.30% were non-families.

Lauderdale County is the location of the W. C. Handy Home and Museum and the Rosenbaum House.

The last Democrat to win the county in a presidential election is Bill Clinton, who won it by a plurality in 1992.