The growth and decay of ocean-island volcanoes are intrinsically linked to vertical movements. While the causes for subsidence are better understood, uplift mechanisms remain enigmatic. Santa Maria Island in the Azores Archipelago is an ocean-island volcano resting on top of young lithosphere, barely 480 km away from the Mid-Atlantic Ridge. Like most other Azorean islands, Santa Maria should be experiencing subsidence. Yet, several features indicate an uplift trend instead. In this paper, we reconstruct the evolutionary history of Santa Maria with respect to the timing and magnitude of its vertical movements, using detailed field work and 40Ar/39Ar geochronology. Our investigations revealed a complex evolutionary history spanning ∼6 m.y., with subsidence up to ca. 3.5 Ma followed by uplift extending to the present day. The fact that an island located in young lithosphere experienced a pronounced uplift trend is remarkable and raises important questions concerning possible uplift mechanisms. Localized uplift in response to the tectonic regime affecting the southeastern tip of the Azores Plateau is unlikely, since the area is under transtension. Our analysis shows that the only viable mechanism able to explain the uplift is crustal thickening by basal intrusions, suggesting that intrusive processes play a significant role even on islands standing on young lithosphere, such as in the Azores.