The Neogene–Quaternary Albegna basin (southern Tuscany, central Italy), located to the south of the active geothermal field of Monte Amiata, hosts fossil and active thermogene travertine deposits, which are used in this study to reconstruct the spatio-temporal evolution of the feeding hydrothermal system. Travertine deposition is controlled by regional tectonics that operated through distributed N-S– and approximately E-W–striking transtensional fault arrays. The geochronological data set (230Th/234U, uranium-series disequilibrium) indicates a general rejuvenation (from >350 to <40 ka) of the travertine deposits moving from north to south and from higher to lower elevations. Negative δ13C and positive δ18O trends with younger deposition ages and lower depositional elevations provide evidence for a change in space and time of the hydrothermal fluid supply, suggesting a progressive dilution of the endogenic fluid sources by increasing meteoric water inputs. Comparison with paleoclimate records suggests increased travertine deposition during humid interglacial periods characterized by highstands of the water table. Travertine deposits of the Albegna basin record the interactions and feedbacks among tectonics, hydrothermalism, and paleoclimate within a region of positive geothermal anomaly during the Quaternary. Our study also sheds light on the neotectonic evolution of the Tyrrhenian margin of central Italy, where hydrothermalism has been distributed along margin-transverse structures during the Pleistocene and Holocene. It is hypothesized that originally upper-crustal, margin-transverse faults have evolved to through-going crustal features during the Quaternary, providing structurally controlled pathways for hydrothermal fluids. We suggest that this was the consequence of a change in the relative magnitude of the principal stress vectors along the Tyrrhenian margin that occurred under a regional stress field dominated by a continuous extensional regime.