[2] It was formed in 1878 from portions of Clay, Harlan, and Perry counties, and named for Preston Leslie, governor of Kentucky from 1871 to 1875.

[7] After resigning the presidency, Richard Nixon made his first public appearance, in July 1978, at the Leslie County dedication of a recreation facility named for him.

County Judge-Executive C. Allen Muncy claimed the Nixon invitation prompted the U.S. Department of Justice to obtain indictments of him and his associates on vote-fraud charges; while on appeal for his conviction, he won renomination in the Republican primary but lost the 1981 general election to independent Kermit Keen.

Of 3,142 counties in the United States in 2014, the Institute for Health Metrics and Evaluation ranked Leslie County 3,120 in the average life expectancy at birth of male residents and 3,130 in the life expectancy of female residents.

Factors contributing to the short, and declining, life expectancy of residents of Leslie county included obesity, smoking, and low amounts of exercise.

[16][17] In 2020, the Robert Wood Johnson Foundation ranked Leslie country 107 of 120 counties in Kentucky in "health outcomes," as measured by length and quality of life.

Leslie's fierce Unionist sympathies, so strong that areas surrounding it contributed more troops to the Union Army relative to population than any other part of the United States,[25] meant that between 1896 and 1928 no Democrat could receive even ten percent of the county's vote,[26] and none received so much as twenty-five percent until Lyndon Johnson managed over 47 percent in his landslide national triumph against Barry Goldwater in 1964.

Despite Goldwater's relatively poor performance, every Republican candidate since the county's formation has obtained an absolute majority in Leslie County, and only William Howard Taft in the divided 1912 election,[26] George H. W. Bush in 1992, and Bob Dole in 1996 have otherwise received under seventy percent for the GOP.