We use δ18O and δ13C of oyster shells, inferred seawater δ18O (δw), and temperature tolerance ranges of modern zooxanthellate coral communities to constrain and model paleo-salinities of marginal-marine waters of the Miocene Lorca Basin, Spain. Salinities ranged from 22 to 32 PSU during growth of coral bioherms and carpets of the Soriana and Parrilla formations, and from 35 to 39 PSU during deposition of the Hondo Formation reef complex. The periods with lower modeled salinities correspond with deltaic and alluvial-fan sedimentation in the area. The modeling is supported by 87Sr/86Sr data and provides new insights into the evolution of the local depositional settings. Departures of Sr-isotope values from the global oceanic curve occur within the intervals with the lowest modeled salinities, and the non-oceanic 87Sr/86Sr preserved in individual oyster shells was probably sourced from uplifted Aquitanian–Burdigalian limestones. 87Sr/86Sr values that plot along the global ocean Sr-isotope curve for the late Miocene indicate a Tortonian age for the upper part of the Soriana Formation and the Parrilla Formation, and a Messinian age for the Hondo Formation. More generally, we demonstrate how the chemical analyses of oyster shells provide additional information regarding short-term oscillations of salinity and temperature of seawater beyond what can be obtained by traditional paleoecological methods.