Developments in nanoscale engineering now allow for molecular scale optimization of reactivity, sorption, and magnetism, among other properties, for advanced, material-based environmental applications, including sorption, separation, and sensing of radionuclides. Herein, we describe novel, monodisperse nanoscale manganese ferrite crystals (MnFe₂O₄) for ultra-high capacity environmental sorption and subsequent separation of uranyl in water. System optimization was explored as a function of nanocrystal (core) composition, surface coating(s), and water chemistry. 11 nm MnFe₂O₄ nanocrystals, which were colloidally stabilized via engineered oleyl-based surface bilayers, demonstrate extreme, yet specific, uranium binding capacities while remaining monomerically stable under environmentally relevant conditions (water chemistries), which are key for application. In particular, MnFe₂O₄ cores with oleyl phosphate (as the outer facing layer) bilayers demonstrate preferential uranium binding of >150% (uranium weight)/(particle system weight) while being highly water stable in elevated ionic strengths/types and pH (up to 235.4 ppm (10.24 mM) of NaCl and 51.3 ppm (1.28 mM) of CaCl₂, in addition to 60 ppm of uranyl, pH 5–9). Further, when normalized for size and surface coatings, MnFe₂O₄ nanocrystals had significantly enhanced sorption capacities compared to Mn₂FeO₄, Fe₃O₄ and manganese oxide core analogs. Mechanistically, we demonstrate that observed uranium sorption enhancement is due not only to thermodynamically favorable interfacial interactions (for both particle and selected bilayer coatings), but also due to significant uranyl reduction at the particle interface itself. Uranium sorption capacities for optimized systems described are the highest of any material reported to date.