Abstract: The separation of bastnaesite from fluorite during the flotation process of rare earth minerals presents significant challenges due to the similarities in their surface chemical properties. This study investigates the effectiveness of polyepoxysuccinic acid (PESA, C₄H₄O₅)_n) as a selective depressant, and assesses its effect on the floatability of bastnaesite and fluorite through both single mineral and actual ore flotation experiments, specifically using magnetic separation of iron tailings from Baiyun Obo. The underlying mechanisms were investigated using Zeta potential measurements, Fourier−transform infrared spectroscopy (FTIR), and X−ray photoelectron spectroscopy (XPS). The results of flotation experiment indicate that, under single mineral flotation conditions with sodium oleate (NaOL) as the collector, recoveries of both bastnaesite and fluorite exceed 90%. When 40 mg/L of PESA is used as an inhibitor, the recovery of bastnaesite reaches 98.65%, while the recovery of fluorite drops to almost zero. In practical ore flotation scenarios, employing P8 as the collector, together with water glass and PESA as the inhibitors, and 2^# oil as the frother, results in a rare earth concentrate with rare earth oxide (REO) and CaO contents of 57.27% and 4.50%, respectively, achieving a recovery rate of 52.10%. The introduction of PESA contributes to an increase of 1.92 percentage points in the REO content of the concentrate, and a reduction of 5.48 percentage points in CaO content compared to conditions without PESA. Mechanistic analyses indicate that the introduction of PESA results in a negative alteration of the Zeta potential of bastnaesite; however, no significant changes are observed in the infrared absorption peaks or the binding energy of the surface atoms. The adsorption occurring on the bastnaesite surface is predominantly characterized as physical adsorption, with limited evidence of chemical adsorption. Consequently, NaOL continues to adsorb on the bastnaesite surface, thereby maintaining its favorable floatability. In contrast, the Zeta potential, infrared absorption peaks, and binding energy of the surface atoms of fluorite show significant changes, suggesting a chemical bonding effect during the adsorption process on the fluorite surface. This effect inhibits the adsorption of NaOL on fluorite, resulting in a marked decrease in its floatability. This study provides new insights into the reagent scheme for effective separation of bastnaesite and fluorite.