Prehistoric activity has been recorded suggesting intermittent settlement activity in the area in the Mesolithic and Bronze Age.  Kilkenny was the capital of the ancient kingdom of Ossory.

In 928 AD. residents close to Dunmore Cave sought refuge there from the Vikings who were seeking to capture them and sell them as slaves. The Vikings set fires to force the people out, but the fires consumed the oxygen and over 1,000 people died there.

Following the  Norman invasion of Ireland,  Strongbow, as Lord of Leinster, established a castle near modern-day Kilkenny Castle. Kilkenny became one of the counties of Leinster in 1210. Kilkenny in Norman times had two townships: Irishtown, and Englishtown which was raised to the status of a city in 1609. The two were united in 1843. The people of Kilkenny are known as “Cats” a symbol of tenacity.

Many parliaments were held in Kilkenny from 1293 to 1408. The English government in Ireland passed the Statutes of Kilkenny in 1367 designed to keep English settlers from integrating with the Irish.

The Confederation of Kilkenny, representing the native Irish and the Anglo-Norman Catholics, functioned from 1642-1648 as an independent Irish parliament.

Following the defeat of the Irish Confederate forces, Oliver Cromwell’s forces attacked the town in 1650, and it surrendered.

In 1320, the first recorded instance of a person being charged with witchcraft in Ireland happened in Kilkenny.

The trial of Alice Kyteler, her son and ten others, for heresy, was of one of the earliest witchcraft accusations in Europe. Alice's maidservant was burned alive at the stake. She was the first case in Ireland's history of death by fire for the crime of heresy as part of Pope John XXII campaign against sorcery.

Prior to the Battle of the Boyne King James of England resided in Kilkenny castle.

The Irish Republican Brotherhood was formed in 1858 by Kilkenny man, James Stephens. The Irish Volunteers in Kilkenny were led by Tom Treacy and Peter DeLoughry.

Thomas MacDonagh, the executed 1916 leader, taught in Kilkenny, launched the Irish Volunteers there, and the MacDonagh shopping mall is named in his honor. Over 30 Kilkenny people were arrested in the wake of the Easter Rising.

W.T. Cosgrave won a by-election for Sinn Fein in Kilkenny in 1917. In May 1922 18 men were killed in a battle in Kilkenny between pro and anti-treaty forces.