The hill above the Quoile was once called Ráth Celtchair - the fort of Celtchar, a hero from the Ulster Cycle of Irish mythology. By the early Christian period, an actual ringfort stood there, and it grew into the capital of the Dál Fiatach, the ruling dynasty of the medieval kingdom of Ulaid. Saint Malachy became Bishop of Down in 1137, administering the see from Bangor while introducing a community of Augustinian canons to the hill at Dún da Lethglas. Malachy and his successors rebuilt and enlarged the cathedral. Then, in February 1177, John de Courcy marched north from Dublin with 300 men and 20 knights and took the town by surprise. The King of Ulster, Ruaidrí mac Duinn Sléibe, tried to retake it and was forced to withdraw. The Anglo-Norman world had arrived.

John de Courcy began building a motte inside the older royal fort, then quickly abandoned it when he made Carrickfergus his Ulster capital instead. But before he left, he rededicated the cathedral to Saint Patrick - linking the saint who had evangelized fifth-century Ireland with the town that now bore his name. Whether Patrick was actually buried here is a question medieval pilgrims did not bother to ask. The relics drew them, the cathedral grew, and the place became Downpatrick - the dún of Patrick - in records that begin to use the form in the early seventeenth century. The cathedral itself was burned by English forces under Edward Cromwell in 1600 and lay in ruins for almost two centuries before being rebuilt. John Wesley preached among the ruins in 1778 and called them noble.

On 21 October 1803, a co-founder of the United Irishmen named Thomas Russell was hanged outside Downpatrick Gaol. He had tried to raise local United Irishmen and Defenders in support of Robert Emmet's rebellion that July, and the rebellion had failed. Russell is buried in the graveyard of St Margaret's Church in Downpatrick, in a plot paid for by his friend Mary Ann McCracken - sister of the Belfast United Irishman Henry Joy McCracken, who had been hanged in 1798 for his role in the earlier rising. McCracken paid for two graves in her life, one for her brother and one for her brother's comrade. The old county gaol where Russell died now houses the Down County Museum, and the building is still known as the place where Russell was hanged.

A mile and a half east of Downpatrick, four stone wells sit in a hollow at Struell. They predate Saint Patrick by centuries and have been used as healing wells since pre-Christian times. People still come. A few miles farther, Saul Church marks the spot where Patrick is said to have preached his first sermon in Ireland - a small twentieth-century church on land traditionally held to be Patrick's own. Each March 17, Downpatrick closes its main streets for the largest Saint Patrick's Day parade in Northern Ireland. The celebration runs cross-community, the way the town itself does. In the 2021 census, 83.6 percent of Downpatrick's 11,545 residents came from a Catholic background, but the parade route passes English Street, Irish Street, and Scotch Street - the four old eighteenth-century thoroughfares that were already in place when the town plan was drawn in 1724.

Inch Abbey, founded by John de Courcy in 1180, ruins beautifully beside the Quoile a mile north of town - the railway runs from Downpatrick out to it. Quoile Castle, a sixteenth-century tower house, stands closer to Strangford. Ballynoe Stone Circle, just south of town, ringed its central mound around 3000 BC. The Mound of Down, on the northwestern edge of the modern town, was an Iron Age earthwork that became a Norman motte and bailey after de Courcy's victory in 1177. The St Patrick Centre is the only permanent exhibition in the world dedicated to the patron saint of Ireland. The cathedral, rebuilt in the eighteenth and nineteenth centuries, holds the slab that pilgrims still touch. Patrick has been here, in one form or another, for fifteen centuries. The town has had longer than that to settle around him.