Intrinsic water-use efficiency (iWUE) of trees is an important component of the Earth’s coupled carbon and water cycles. The causes and consequences of long-term changes in iWUE are, however, still poorly understood due to the complex interplay between biotic and abiotic factors. Inspired by the role calcium (Ca) plays in plant transpiration, we explore possible linkages between tree ring-derived iWUE and Ca availability in five central European forest sites that were affected by acidic air pollution. We show that increasing iWUE was directly modulated by acid air pollution in conjunction with soil Ca concentration. Responses of iWUE to rising atmospheric CO2 concentrations accelerated across sites where Ca availability decreased due to soil acidity constraints, regardless of nitrogen and phosphorus availability. The observed association between soil acidity, Ca uptake, and transpiration suggests that Ca biogeochemistry has important, yet unrecognized, implications for the plant physiological upregulation of carbon and water cycles.