The ridge is part of the system of eskers, long gravel and sand formations deposited by meltwater beneath retreating ice sheets, that once served as natural causeways across the Irish midlands. Where the ridge met the river, a ford existed, and around that ford a town eventually grew. The Irish name Áth Luain, meaning the ford of Luain, records this origin plainly, and the logic of the location proved so compelling that every major route linking the eastern provinces with the west, including eventually the Dublin to Galway railway, has crossed at this same point since the Middle Ages.

The earliest traces of human activity here are five cross-inscribed slabs, four of them found in the graveyard of the Franciscan Friary on the east bank of the Shannon, dating from between the mid-eighth and eleventh centuries. One of these slabs appears to commemorate a King of Connacht, which points to an Early Christian monastery of some standing at Athlone, though a suggestion that the slabs were brought from Clonmacnoise has occasionally complicated the picture. By 1001, the Annals of Ulster record that a causeway at Athlone was built jointly by Mael Sechlainn, King of Midhe, and Cathal son of Conchobhar, King of Connacht, an early sign that control of the crossing required cooperation or contention between powerful rivals. Through the twelfth century, the O'Conor kings of Connacht treated the ford as their essential bridgehead eastward: Toirdhealbhach O'Conor built a bridge here in 1120 and an earthwork fortification in 1129 to defend it, only for both to be repeatedly destroyed by the Ua Máel Sechlainn kings of Meath and rebuilt again. By 1168 the Annals of the Four Masters record that Ruaidhri Ua Conchobhair had a royal residence at Athlone from which raiders carried away gold, clothing, and many cattle. The Cluniac priory of Saints Peter and Paul was established on the west bank around 1158, though almost nothing of it survives above ground today. When the Anglo-Normans arrived, the importance of the location was immediately apparent. Geoffrey de Costentin received a grant of land adjoining Athlone around 1200 and was probably responsible for an early motte castle, a raised earthen mound with a timber fortification on top, built between 1191 and 1199. King John's visit to Ireland in 1210 accelerated matters considerably: his justiciar, John de Grey, Bishop of Norwich, oversaw the construction of a new stone castle and bridge that year, with the apparent ambition of making Athlone a joint seat of English administration alongside Dublin. By 1221 Henry III had granted the town an annual eight-day fair to be held at the castle, and references to mills and a growing settlement follow through the 1220s and 1230s. The Franciscan friary church that stands on the south side of the town today dates in its current form to the 1680s, a rebuilding after the medieval friary was destroyed in 1567 to 1568 and its site leased away.