Regional tropospheric water balance depends on local mixing rates, moistening and precipitation efficiency associated with cloud processes, and large‐scale moisture advection. Conventional data sets are insufficient to disentangle how these processes affect the regional humidity, and models are limited by their need to parameterize many of the pertinent mechanisms, including precipitation efficiency, evaporation of cloud condensate, and mixing rates. This study provides new insight by constraining a Lagrangian mass balance model with satellite measurements of specific humidity and the HDO/H2O ratio in water vapor. Seasonal estimates of mixing rates, moistening efficiency, isotopic composition of source waters, and effective isotopic fractionation in clouds are calculated. Analysis shows that the water source is dominated by cloud evaporation in the dry subtropics, subcloud rainfall recycling in the humid subtropics, and convective detrainment and postcondensational exchange during tropical monsoons. Moistening efficiency is shown to be as twice as strong over the wintertime subtropics as over other regions. Over monsoonal areas, however, moistening efficiency decreases during times of most intense mixing, since postcondensational exchange and convective recycling effects act to dehydrate and isotopically deplete the local water sources. A robust relationship is found between precipitation efficiency derived from rainfall profile measurements and differences in effective and equilibrium isotopic fractionation rates, suggesting that isotopic observations might enable estimates of this illusive parameter to be inferred directly. In spite of the simple modeling framework employed, the results provide insight in to the gains that can be expected by assimilating satellite observations of isotope ratios into more comprehensive, isotope‐enabled general circulation models.