Named for Thomas Jefferson, who was governor of Virginia at the time,[4] it was one of Kentucky's nine original counties on June 1, 1792.

In 1778, during the American Revolutionary War, George Rogers Clark's militia and 60 civilian settlers, established the first American settlement in the county on Corn Island in the Ohio River, at head of the Falls of the Ohio.

Richard Mentor Johnson, the 9th Vice President of the United States, was born in Jefferson County in 1780, while the family was living in a settlement along the Beargrass Creek.

[5] The last major American Indian raid in present-day Jefferson County was the Chenoweth Massacre on July 17, 1789.

Prior to the 2003 merger, the head of local government was the County Judge/Executive, a post that still exists but now has few powers.

[6] Local government is effectively now led by the Mayor of Louisville Metro, Craig Greenberg.

The highest point is South Park Hill, elevation 902 feet (275 m), located in the southern part of the county.

The functions formerly served by the county government for the towns were assumed by Louisville Metro.

The county voted "No" on 2022 Kentucky Amendment 2, an anti-abortion ballot measure, by 71% to 29%, outpacing its support of Joe Biden during the 2020 presidential election.