Atmospheric relative humidity (RH) is an important parameter affecting vegetation yet palaeoproxies for RH are scarce and difficult to calibrate. Here we use triple oxygen ( 17 O and 18 O) and hydrogen (D) isotopes of structurally bounded gypsum hydration water (GHW) extracted from lacustrine gypsum to quantify past changes in paleo-atmospheric RH. An evaporation *Manuscript Click here to view linked References isotope mass balance model is used together with Monte Carlo simulations to determine the range of climatological conditions that simultaneously satisfy the stable isotope results of GHW, and with statistically robust estimates of uncertainty. We apply this method to reconstruct the isotopic composition of paleo-waters of Lake Estanya (NE Spain) and changes in atmospheric RH over the last glacial termination and Holocene (from ~15 to 0.6 cal. kyrs BP). The isotopic record indicates the driest conditions occurred during the Younger Dryas (YD; ~12-13 cal. kyrs BP). We estimate a RH of ~40-45% during the YD, which is ~30-35% lower than today. Because of the southward displacement of the Polar Front to ~42 o N, it was both windier and drier during the YD than the Bølling-Allerød period and Holocene. Mean atmospheric moisture gradually increased from the Preboreal to Early Holocene (~11 to 8 cal. kyrs BP, 50-60%), reaching 70-75% RH from ~7.5 cal. kyrs BP until present-day. We demonstrate that combining hydrogen and triple oxygen isotopes in GHW provides a powerful tool for quantitative estimates of past changes in relative humidity.