Clay minerals have been proposed for the potential retention of the high-level radioactive wastes in deep geological repositories. The retention of uranium (U(VI)) and europium (Eu(III)) onto well-characterized sepiolite was elucidated by using microscopic adsorption, spectroscopic techniques and surface complexation modeling. The results of macroscopic adsorption experiments showed that the uptake of U(VI) and Eu(III) onto sepiolite significantly increased with increasing pH 4.0–7.0, whereas the decrease adsorption of U(VI) at pH>7.0 and in the presence of carbonate (10−3mol/L) was attributed to the electrostatic repulsion. The chemical affinity of U(VI) with sepiolite was stronger than that of Eu(III) with sepiolite in terms of batch desorption tests. Based on the EXAFS spectra analysis, the interatomic distances of U–Si at ∼3.16Å was observed in U(VI)/sepiolite systems, which indicated that the inner-sphere surface species were coordinated on SiO4 tetrahedra via bidentate configuration. The U–C shell at ∼2.9Å in the presence of carbonate revealed the U(VI)-carbonate ternary complexes at sepiolite–water interface. The results from the three common surface complexation models (SCMs), including constant-capacitance model (CCM), diffuse-layer model (DLM), and triple-layer model (TLM), can give an excellent fit to the experimental data with the bidentate edge-sharing (E2, >SO2M(n−2)+), bidentate corner-sharing (C2, (>SO)2M(OH)2(n−4)+) and >SOMCO3(n−3)+ inner-sphere surface complexes in ambient environments. However, the second ternary surface complex >SOCO2M(n−1)+ was determined in the presence of carbonate. The findings presented in this study are significant toward the description and predication of fate and transport of radionuclides at the water–mineral interface in the natural environment.