The Lisgoole site began as an old Irish monastery dedicated to St Aid, almost certainly a wooden enclosure on the lakeshore in the early medieval centuries. In either 1106 or 1145, depending on which source you trust, it was reconstituted under the Canons Regular of St Augustine and dedicated by McNoellus Mackenlef, King of Ulaid. From then on the Abbey Church of St Peter, St Paul, and St Mary appears in the medieval Irish records under a parade of slightly varying spellings: Lesa Gabail in 1275, Lisngabail in 1306, Leasa Gabhail in 1348, Lis Gabhail by 1425. The fluid orthography is itself evidence that this was a major site whose name passed mouth to mouth across the centuries before the spelling stabilised.

In 1360 the abbey was burned, along with the monasteries at Devenish, Roscommon, Sligo, Fenagh, and Drumlias, in one of the periodic conflagrations that swept Irish ecclesiastical sites in the late medieval period. Lisgoole was soon restored. Records during the reign of Richard II of England note Einri Mac Caba as abbot, with a wife and a daughter named Aine, a reminder that medieval Irish abbots were often hereditary figures embedded in local clan politics, more chieftain than celibate cleric. The abbey escaped the worst of the Reformation period, but its monastic community gradually dwindled. In 1583, the last abbot, Cahill McBrien McCuchonnaght Maguire, drew up an agreement to hand the abbey and its lands over to the Franciscan order. The Franciscans would maintain a presence here for the next two centuries.

Micheal O Cleirigh, born around 1590 near Donegal town and trained as a Franciscan in Louvain, returned to Ireland in 1626 with a specific commission: to collect and copy the surviving manuscripts of Gaelic Ireland before they vanished. For seven years he travelled from monastery to monastery doing exactly that. In 1631 he stopped at Lisgoole and, together with O'Mulcrony, Cucoigry O'Glery, O Duigenan, and Gilla Patrick O'Lennon, produced a fresh recension of the Lebor Gabala Erenn. The text traces the supposed waves of invasions of Ireland from the time of Noah onwards, through the Fomorians, the Nemedians, the Fir Bolg, the Tuatha De Danann, and the Milesians. It is part myth, part genealogy, part scholarship, all in Old Irish. The same five scholars would, three years later, complete the Annals of the Four Masters at Bundrowes in County Donegal, the great compendium of Gaelic Irish history.

In 1644 Connor Maguire, Lord Maguire of Enniskillen, was hanged at Tyburn in London for his role in the 1641 Irish Rebellion. His last will and testament was kept in a strong box in the custody of the Franciscans at Lisgoole, and among its bequests was twenty pounds to the abbey for prayers for his soul. By 1698 the abbey had passed out of Franciscan hands altogether, sold to a Mr Thomas Smith by Charles Wallis and his wife, the successors of the Earl of Huntingdon. A small handful of monks continued worshipping into the eighteenth century, but their work running outlying parishes drew them away and the community finally extinguished itself.

The building that stands today is a large Georgian house with a battlemented tower attached at one end, set in substantial grounds along the southern shore of the upper lough. In the nineteenth century the building was used as an orphanage, the kind of institution that scattered across rural Ireland in the post-Famine decades. During the Second World War, American army units took it over. The 109th Medical Battalion of the 34th Infantry Division arrived in 1942. The 8th Medical Battalion of the 8th Infantry Division was there from December 1943 until 1944, preparing for the campaigns in Normandy and beyond. The grounds saw GI ambulances and stretcher drills among the same trees that once shaded medieval scriptoria. The house is now privately owned. The five scholars at the table in 1631 would not recognise the rooms. They would, perhaps, recognise the lake outside the window.