The oldest building in town is Enniskillen Castle, raised by Hugh Maguire the Hospitable, who died in 1428. An earthwork called the Skonce on the lakeshore may be the remains of an even earlier motte. The castle's wonderful watergate, a twin-turreted little riverside fortification that has become the town's symbol, was added around 1580 by Cu Chonnacht Maguire. The lough level was later lowered, leaving the watergate stranded above dry stones, but the silhouette remains. The castle was besieged three times in 1594 to 1595 during the Nine Years War. Captain Dowdall took it for the English in February 1594. The Maguires retook it after defeating an English relief column at the Battle of the Ford of the Biscuits on the Arney River, and held it until 1598. It was not finally captured for the Crown until 1607, on the eve of the Plantation.

William Cole, a Devonshire soldier appointed by James I in 1612, built the modern town. Installed as Constable, Cole strengthened the castle wall and raised a 'fair house' on its foundation as the centre point of the new county town. The first Protestant parish church went up on the hilltop in 1627. By 1630 around 180 inhabitants lived on the island, mostly English and Scottish settlers. The Royal Free School of Fermanagh, the ancestor of Portora Royal School, moved onto the island in 1643. The first bridges across the Erne were drawbridges; permanent bridges did not arrive until 1688. In the Williamite war of 1689 to 1691, Enniskillen and Derry were the two Ulster garrisons that refused to declare for James II, and the Enniskilleners' victory at the nearby Battle of Newtownbutler became part of the founding mythology of Protestant Ulster. Two British Army regiments were raised here: the Royal Inniskilling Fusiliers and the 6th (Inniskilling) Dragoons. Enniskillen Castle still appears on both regimental cap badges.

On the morning of 8 November 1987, a Provisional IRA bomb hidden in the Reading Rooms behind the cenotaph on Belmore Street exploded as a Remembrance Sunday parade approached. Eleven people died at the scene. A twelfth man, Ronnie Hill, fell into a coma he never came out of, dying in December 2000. Sixty-three were injured. Among the survivors was Gordon Wilson, who lay in the rubble holding his daughter Marie's hand as she died. That evening, in a BBC interview from his hospital bed, Wilson said: 'I bear no ill will. I bear no grudge.' He went on to become a peace campaigner and a member of Seanad Eireann. He lived for the rest of his life on Cooper Crescent in this town. Bill Clinton opened the Clinton Centre on the site of the bombing in 2002. Enniskillen has chosen to remember publicly, and the memorial added in 1991 stands beside the Great War names without claiming any greater grief.

Walk Enniskillen and the place keeps producing names. Oscar Wilde sat in classrooms at Portora Royal School from 1864 to 1871, his name still cut into a window frame there. Samuel Beckett followed at the same school in 1920. Henry Francis Lyte, the curate who wrote the hymn Abide With Me in 1847, was a Portora pupil too. James Gamble, who emigrated to Cincinnati and co-founded Procter and Gamble in 1837, was educated here. So was the Jesuit priest John McElroy, who founded Boston College in 1863. The town produced Victoria Cross winners Eric Bell and Henry Hartigan, the artist William Scott, the actor Adrian Dunbar, the singer Neil Hannon of The Divine Comedy, the actor Charles Lawson of Coronation Street, the footballer Kyle Lafferty with 89 Northern Ireland caps, and the Olympic 100m gold medallist Robert Kerr, who took the prize for Canada in 1908. For a town of 14,086 people at the 2021 census, the export list is enormous.

Enniskillen now lives mostly off its surroundings. Castle Coole, the Wyatt-designed Palladian palace of 1797, is a mile outside town. Florence Court, the eighteenth-century National Trust mansion famous for the original Florence Court yew, lies eight miles southwest. Monea Castle and Portora Castle add Plantation-era ruins to the rota. The Marble Arch Caves, the Cliffs of Magho, and the Cuilcagh Mountain Global Geopark are all within an hour's drive. The Happy Days arts festival, celebrating the work of Samuel Beckett, has run in the town since 2012. And in June 2013, the Lough Erne Resort on the lakeshore hosted the 39th G8 summit, with David Cameron, Barack Obama, Angela Merkel, and Vladimir Putin all checking in. It was the largest diplomatic gathering ever held in Northern Ireland. By then the town had spent enough decades rebuilding to be ready to host the world without flinching.