The study of the history of the first excavations on prehistoric Therasia in the nineteenth century, which were carried out in the context of contemporary scientific interest in the volcanic eruptions of Santorini, has led to the systematic archaeological investigation of the island from 2007 onwards. The intensive archaeological surface survey, the geological survey of the geological structure and palaeotopography of Therasia, and geophysical investigations, undertaken in conjunction with the ongoing excavation of the prehistoric settlement at the site of Panaghia Koimisis at the southern end of modern Therasia, have created the conditions for a more comprehensive approach to the archaeological landscape of the island. Based on the results from the excavation trenches in the south and south-east terraces of the Koimisis hill, which have been excavated down to the virgin soil, we present findings on the organisation, architecture and habitation phases of the Koimisis settlement. The site emerges as an important settlement located on the imposing hilltop rising on the west side of the pre-eruption Santorini caldera in the Early Bronze Age, with a long period of habitation to the end of the Middle Cycladic period, when it was definitively abandoned. The excavation of the settlement provides new information on its architecture and spatial organisation during the Early and Middle Bronze Age, completing the picture from Akrotiri, whose early phases are preserved in a piecemeal fashion under the buildings of the Late Cycladic town.