Understanding the structure-property relationship and the way in which catalysts facilitate polysulfide conversion is crucial for the rational design of lithium-sulfur (Li-S) battery catalysts. Herein, a series of NiAl2O4, CoAl2O4, and CuAl2O4 spinel oxides with varying Ni2+, Co2+, or Cu2+ tetrahedral and octahedral site occupancy are studied as Li-S battery catalysts. Combined with experimental and theoretical analysis, the tetrahedral site is identified as the most active site for enhancing polysulfide adsorption and charge transfer. This work demonstrates the geometric configuration dependence of spinel oxides for polysulfide conversion and highlights the role of the molecular orbital in determining the activity of cations in different geometries, thereby providing new insights into the rational design of Li-S battery catalysts.