Bis(2,4,dithiophosphinic acid, commonly referred to as HBTMPDTP or Cyanex301, is a sulfur-donating ligand that shows considerable promise in the challenging task of separating trivalent actinides (An 3+ ) from lanthanides (Ln 3+ ). Although its effectiveness has been established, the specific molecular details about the preference of HBTMPDTP for americium over europium have remained a mystery, puzzling researchers for over two decades. This study presents a comprehensive, dualdriven separation mechanism for this complex system combining experimental and theoretical approaches. A critical finding is the increased covalency in An−S bonds compared to Ln−S bonds, which plays a significant role in HBTMPDTP's intrinsic selectivity for An 3+ over Ln 3+ . This leads to the formation of distinct An 3+ and Ln 3+ species, enhancing the ligand's actinide selectivity. Additionally, it provides crucial insights into the coordination chemistry of felements with sulfur-donating ligands, thereby deepening our understanding of this intricate field.