Synoptic weather events are known to strongly influence the isotope composition ofprecipitation in continental locations. In this study, we present hourly values of water vaporisotopologues (HDO and H218O) measured over a 30 day period in locally extreme weatherconditions, including Santa Ana winds and winter rainstorms, in San Diego, California,USA. We investigate how atmospheric and hydrological processes influence HDO andH218O using an isotope-enabled GCM model (IsoGSM). Combining measurements andIsoGSM simulation, we demonstrate that convective mixing of marine and continental airmasses are responsible for the isotopic variation of near-surface water vapor in this coastallocation. The isotopic variability is most pronounced during Santa Ana winds. The SantaAna winds represent a unique boundary layer condition in which atmospheric mixingbecomes the process that dominantly controls the changes in the isotopic compositionrelative to air humidity. We demonstrate that a two-source mixing approach (Keeling plot)can reliably be used to estimate the isotopic composition of the source moisture, and fromthat, to infer the location of the moisture origin that contributes to the atmospheric moisturecontent in southern California. The present study is unique because it combines large-scaleisotope GCM modeling with a robust and high-resolution isotope data set to disentangle thecontrol of atmospheric and hydrologic processes on the atmospheric humidity in anextratropical climate. Our results demonstrate the utility of using single-point, ground-basedisotope observations as a complementary resource to existing satellite isotopemeasurements for constraining isotope-enabled GCMs in future investigation ofatmospheric water cycle.