Abstract: The growing need for sustainable nuclear energy production has brought increasing attention to the back-end management of spent nuclear fuel, particularly the handling of long-lived minor actinides such as americium (Am). As one of the most radiotoxic elements in high-level radioactive waste, americium poses significant environmental and safety challenges due to its long half-life and high α radiation. A promising strategy to mitigate these risks is to isolate Am from other fission products, especially the chemically similar lanthanides (Ln), and subject it to transmutation. However, the nearly indistinguishable chemical behavior between Am(Ⅲ) and trivalent lanthanides, such as neodymium (Nd) and europium (Eu), makes their separation extremely challenging through conventional solvent extraction methods. In this study, an oxidation-based approach was developed to overcome the limitations of traditional separation techniques. The method begins by oxidizing Am(Ⅲ) to Am(Ⅵ) in an aqueous nitric acid solution using sodium bismuthate (NaBiO₃) as the oxidant. This high oxidation state of Am, which is significantly less prone to extraction than Ln(Ⅲ), enables selective separation. Upon contact with an organic phase containing extractants, Am(Ⅵ) is partially reduced to Am(Ⅴ), a linear oxo-cation with unique coordination properties that further distinguish it from spherical Ln(Ⅲ) ions. Two extractants, di(2-ethylhexyl) phosphoric acid (HDEHP) and trialkylphosphine oxide (TRPO), were employed independently to evaluate their separation efficiencies. The results show that both extractants achieve high selectivity, with single-stage separation factors for Nd/Am and Eu/Am exceeding 1 000 under optimized conditions. The effects of contact time, extractant concentration, and aqueous phase acidity were systematically investigated. It is found that TRPO displays excellent kinetic stability and wider acid tolerance, while HDEHP is more effective at low nitric acid concentrations. Additionally, Eu exhibits slightly higher extractability than Nd due to its the higher atomic number and stronger affinity for these extractants. To extend the applicability of the oxidation-extraction process across a wide acidity spectrum, a synergistic system combining HDEHP, TRPO, and N,N,N′,N′-tetraoctyl diglycolamide (TODGA) was constructed. Each extractant covers a different optimal acid range—HDEHP of 0.001-0.1 mol/L HNO₃, TRPO of 0.2-0.5 mol/L, and TODGA of 1.0-5.0 mol/L. The integrated system enables effective Am/Ln separation across the entire 0.001-5.0 mol/L HNO₃ range, with separation factors remaining above 1 000 throughout. The stability of Am(Ⅴ) was confirmed by UV-Vis spectroscopy, which shows rapid reduction of Am(Ⅵ) to Am(Ⅴ) in both extractant systems, with notably prolonged stability in the TRPO system. This research presents a significant advancement in the field of actinide-lanthanide separation. The ability to maintain high separation efficiency through oxidation state control and tailored extractant selection opens new pathways for minor actinide partitioning and transmutation technologies. Moreover, the method’s robustness, broad acidity applicability, and high selectivity make it a promising candidate for future industrial applications.