The area that became Boyle County was one of the first areas to be settled in what was then Kentucky County, Virginia. As early as 1774, James Harrod erected a cabin in Danville and by 1785 Danville became Kentucky's first seat of government. A courthouse, jail and meetinghouse were built and the town continued to grow. In 1787 the town of Danville was established by the Virginia legislature. The area was still bound to Virginia laws and several citizens of the area formed a political club that advocated the need for a convention to discuss statehood. After ten constitutional conventions, held between 1784-1792, at the courthouse in Danville, Kentucky became the 15th state on 1 June 1792. Isaac Shelby, a Revolutionary War hero who made his home just outside of Danville, became the state's first governor.

Danville, known as the "City of Firsts" was home to the first post office west of the Allegheny Mountains. The first mail was delivered on 3 November 1792.

The first brick schoolhouse west of the Alleghenies was built in Danville circa 1820.

Dr. Ephraim McDowell made medical history on Christmas morning 1809 when he successfully removed a twenty-two-and-a-half pound ovarian tumor from Jane Todd Crawford without the benefit of anesthetic or antisepsis.

Penn's Store in the Forkland area of the county is the oldest country store in America in continuous ownership and operation by the same family. It has been a store site since 1845 and in continuous ownership and operation by the Penn family since 1850.

Perryville, established as a fort in 1781, was the site of the largest Civil War battle in Kentucky.