Effective, post-accidental management needs an accurate understanding of the biogeochemical behavior of radionuclides in surface environments at a regional scale. Studies on stable isotopes (element homologs) can improve this knowledge. This work focuses on the biogeochemical behavior of stable cesium (Cs) along a major European fluvial-estuarine system, the Gironde Estuary (SW France). We present results obtained from (i) a long-term monitoring (2014–2017) of dissolved (Csd) and particulate (Csp) Cs concentrations at five sites along the freshwater continuum of the Garonne watershed, (ii) Csd and Csp concentrations during four oceanographic campaigns at contrasting hydrological conditions along longitudinal profiles of the estuarine system, (iii) a 24 h cycle of Csp at the estuary mouth, and (iv) a historical trend of Cs bioconcentration in wild oysters at the estuary mouth (RNO/ROCCH, 1984–2017). In addition, we model the partitioning of Cs within the estuarine environment for clay mineral interactions via PhreeqC. At fluvial sites, we observe a geogenic dependence of the Csp and a seasonal variability of Csd, with a downstream increase of the solid-liquid partitioning (log10 Kd values from 3.64 to 6.75 L kg−1) for suspended particulate matter (SPM) < 200 mg L−1. Along the estuarine salinity gradients, Cs shows a non-conservative behavior where fresh SPM (defined as Cs-depleted particles recently put in contact with Csd) act as a Cs sink during both flood and low discharge (drought) conditions. This sorption behavior was explained by the geochemical model, highlighting the relevance of ionic strength, water and SPM residence times. However, at high salinities, the overall log10 Kd value decreases from 6.02 to 5.20 for SPM ∼300–350 mg L−1 due to the Csd oceanic endmember. Despite wild oysters showing low bioconcentration factors (∼1220 L kg−1) at the estuary mouth, they are sensitive organisms to Cs fluxes.