A mass balance of the naturally occurring short-lived radium isotopes (223,224Ra) in the Venice Lagoon was conducted by an integrated approach combining the directly estimated individual Ra contributions and hydrodynamic model results. Hydrodynamic data allows for the calculation of the Ra mass balance in sub-sections of the Venice Lagoon (boxes), which are characterized by physically homogeneous properties, instead of investigating the entire lagoon. Utilizing this method, both the seasonal and the spatial variability of the submarine groundwater discharge in the Venice Lagoon have been estimated. Between 14–83 × 109 L d− 1 of water were calculated to flow across the sediment–sea interface, corresponding to 5–28 times the mean annual river input. The submarine groundwater discharge estimates were correlated with the residence time calculation to better understand spatial and seasonal variation.