Pettigo is bisected by the Termon River, which forms part of the border between the Republic of Ireland and Northern Ireland. The portion of the village in County Fermanagh is officially called Tullyhommon but locally known as High Street, because it sits on a hill overlooking the rest. The Republic side contains Main Street, Mill Street, and Station Street, all converging at The Diamond at the centre. Until the late 1700s, the area was known as An Tearmann, meaning a place of sanctuary. The modern names Pettigo and Paiteagó derive from the Latin protectio, a translation of the Irish An Tearmann. Sanctuary is more than a name here. The lands around Lough Derg were understood for centuries to be a place where anyone in trouble could find protection.

St Patrick's Purgatory, on Station Island in Lough Derg, has been receiving pilgrims continuously for well over a thousand years. The three-day pilgrimage involves fasting, walking barefoot, praying through the night in the basilica, sleeping in dormitories, and eating one daily meal of dry toast, oatcakes, and black tea. The popularity of the pilgrimage built much of Pettigo's economy during the twentieth century, when tens of thousands of pilgrims a year passed through the village on their way to and from the lake. Bus Éireann seasonal route 486 still ferries pilgrims between Ballyshannon, Pettigo, and Station Island. Although numbers have declined from their mid-century peak, the pilgrimage remains one of the most distinctive religious practices in Western Christianity, and Pettigo remains its terrestrial doorway.

Pettigo Mill stands on the Termon River and dates at least to 1767, when it first appears on maps, though it is probably older. The Leslie family of County Monaghan, who controlled the Pettigo estate until the early twentieth century, built it as a cloth mill, producing woollen cloth. It also ground oats and other grains. During the Great Famine of 1845-1846, the mill ground maize sent through the port of Ballyshannon to feed the starving. After the Enniskillen and Bundoran Railway arrived in 1866, the mill diversified. It became a saw mill as well as a grain mill, and its specialty product was twelve-egg boxes. Eggs were sent by train to Belfast, Dublin, England, and Scotland. The egg boxes mattered economically because many people in Pettigo depended on their egg money to buy groceries. The railway closed in 1957 and the mill's heyday ended with it.

In 1925, the Irish Boundary Commission considered redrawing the border between the new Irish Free State and Northern Ireland. Pettigo was a candidate for transfer to Northern Ireland because of its mixed Protestant and Catholic population and its awkward geographic position straddling the existing line. Had the Commission's recommendations been enacted, Pettigo would have ended up entirely in the United Kingdom. The recommendations were not enacted. The border stayed where it was. For decades afterwards, this had consequences few border villages anywhere else in Europe experienced. The Troubles brought British Army roadblocks closing many of the small cross-border roads, cutting Pettigo off from its rural hinterland in Fermanagh and Tyrone. Most of those roads have reopened. The village is still bisected by a border that almost vanished and then almost moved.

Moya Doherty, co-founder of Riverdance, is from Pettigo. The show that began as a seven-minute interval act at the 1994 Eurovision Song Contest in Dublin grew into one of the most successful theatrical phenomena in modern history, touring globally for three decades. The Pettigo History Trail, with thirty plaques scattered round the village, tells Doherty's story alongside other local figures: General Charles Barton, who lived at the Waterfoot estate; Sir Sidney Barton, who served as British Minister to Ethiopia in the 1930s; the poet John Kells Ingram; the actor Seán McGinley; and Basil McIvor, a Northern Ireland politician who pioneered integrated education. The plaques also note the village's connection to the John Ford film The Quiet Man, and a tree planted to commemorate the Crimean War. For a village of well under a thousand people, Pettigo punches considerably above its weight.

Just outside Pettigo stands Termon McGrath Castle, also called Castle McGrath, a Gaelic towerhouse built around 1611 at the start of the Plantation of Ulster. It was probably commissioned by James McGrath, son of the Most Reverend Miler McGrath, the Church of Ireland Archbishop of Cashel and one of the more peculiar figures in Irish religious history. Miler had been a Franciscan friar, then Bishop of Down and Connor under Pope Pius V, before defecting to the Church of Ireland and accumulating an extraordinary collection of Protestant bishoprics. The castle had an escape tunnel leading down to the Belaut River, suggesting its builders expected trouble. The Leslie family of Monaghan later bought the castle and the surrounding estate. The towerhouse still stands today, a reminder of the unsettled centuries when Gaelic and Anglo-Irish power overlapped uneasily across this hilly country.