It derives from a tavern sign on Cook Street, near which an earlier chapel quietly operated during the Penal era, when Catholic worship in Dublin was conducted with considerable discretion. That earlier building collapsed on a Sunday, killing a number of people who had gathered to hear a sermon, and the story of the place only grows stranger from there.

The Franciscan presence in this part of Dublin stretches back to somewhere between 1615 and 1620, though as the historian N. Donnelly noted in his 1904 study of Dublin's Catholic chapels, it was at first migratory in character, moving from house to house. Adam and Eve Chapel in its more settled form appears to date from around 1714 or 1715. The building that collapsed was adapted for Franciscan use by a Father Francis Walsh, and it was Sylvester Lloyd, then Titular Bishop of Waterford and Guardian of the Franciscan Friars in Dublin, who oversaw its rebuilding. By 1749, following further repairs and alterations, the chapel measured 80 feet in length by 20 and a half in width, and a detailed contemporary description survives: two galleries, a choir, a preacher's rest room behind the pulpit, and a small altar funded by the Freizemongers of High Street, with the pew gallery on the opposite side paid for entirely by a Major Stafford. Immediately to the east, separated only by a brick wall, stood Rosemary Lane Chapel, a parochial church that had begun life around 1670 as a rented stable in Skipper's Alley. That stable fell in 1728, was replaced by another on Rosemary Lane, and was later rebuilt as a proper chapel around 1740 through the efforts of Dr John Clinch, the Parish Priest. The 1749 description of Rosemary Lane Chapel notes one curiosity: it was the only chapel in Dublin without a tabernacle on the altar. Both chapels appear on John Rocque's 1756 map of the city. In 1830, ground adjoining the old Adam and Eve site was leased from Ambrose Leet of No. 4 Merchant's Quay to the Franciscans, and in 1832 they demolished the 1749 chapel and built the present Church of St Francis of Assisi across the combined footprint of both earlier buildings.

The church sits on Merchant's Quay, facing the River Liffey, and retains its entrance from Cook Street as well, a dual-access arrangement that has existed since the 1832 rebuilding. Visitors familiar with the area may walk past it regularly without registering its layered past. The Cook Street entrance in particular gives some sense of how the earlier, more furtive chapels might have been approached, tucked away from the main quayside. Inside, the building is still an active Franciscan church, open for daily Masses, and the congregation is one of the longest-continuous Catholic communities in the city.