Laid out by General Samuel Hopkins and Thomas Allen, the city of Henderson's birthday is considered to be April 6, 1797.  It was originally known as the "Red Banks," to the Native Americans, because of the red clay soil that was found on the banks of the river.  In 1810 Henderson was incorporated as a town.

Below is a timeline of important dates throughout Henderson's history.

1810:  John James Audobon establishes his business in Henderson, KY.  Ultimately his endeavor fails and he moves on to begin his research for his portfolio now known as Birds of America.

1811:  Philip Barbour erects a one-story tobacco, hemp, cotton and pork warehouse.

1835:  The first case of small-pox in the area to be recorded appears in a local tavern.

1842:  (1)  The first sanitary act since the establishment of the town is passed.
(2)  Elizabeth Blackwell takes a teaching position at Henderson Seminary, one of the region's first schools.  Blackwell later becomes the first woman doctor in the United States.

1847:  The Old Hospital is built on the riverfront.

1860:  Streets along the gas main are lit with gas for the first time.

1863:  The George Delker Company begins manufacturing carriages.  The company continues the business until 1922 when it changes it to manufacturing furniture.

1885:  C. C. Givens moves his newspaper, The Gleaner, to Henderson.  Its name is published as the Henderson Morning Gleaner.

1887:  Mary Towles Sasseen, a Henderson teacher, chooses April 20th as a day to celebrate mothers.  Though Mother's Day is not a holiday until 1914, eight years after Sasseen's death, she is officially recognized as the founder of Mother's Day in 2004.

1892:  Blues composer W.C. Handy visits Evansville and Henderson.  Handy meets and marries Elizabeth Price in Henderson and spends nearly a decade in the area.

1937:  The Great Flood devastates the Ohio River Valley, severely damaging surrounding towns but relatively sparing the town of Henderson.  The river rises just under fifty-four feet during the flood.

1946:  "2 Chicago Gangsters Nabbed in Henderson."  The Gleaner proclaims that the FBI has discovered George "Bugs" Moran and Virgil Summers, two mobsters and bootleggers, have been hiding in Henderson.  They are captured and charged for armed robbery.

1990:  W.C. Handy Blues and barbecue Festival is established.  It is one of the largest blues festivals in the United States.