Abstract: To enhance the utilization of industrial solid wastes and improve the stabilization efficacy of expansive soils, this study employed fly ash as the precursor, with phosphogypsum and sodium hydroxide (NaOH) as activators. The Box-Behnken Design response surface methodology (RSM) was adopted to optimize the proportions of fly ash, phosphogypsum, and NaOH. The stabilization mechanisms and microstructural evolution of the soil were systematically investigated. Experimental results revealed that the optimal mixture ratio was 18% fly ash, 8% phosphogypsum, and 2.8% NaOH. The unconfined compressive strength (UCS) of stabilized soil reached 0.65 MPa at 7 days and 0.79 MPa at 28 days. RSM optimization further refined the ratio to 17.978% fly ash, 7.036% phosphogypsum, and 3.043% NaOH, yielding UCS values of 0.67 MPa (7d) and 0.83 MPa (28d). The minimal deviation between predicted and experimental results validated the accuracy and reliability of RSM for mixture design. Microscopic analysis identified ettringite (AFt), calcium silicate hydrate (C-S-H), and calcium aluminosilicate hydrate (C-A-S-H) as the primary hydration products at both curing ages. The hydration products effectively filled and encapsulated soil pores, enhancing compactness and reinforcing the skeletal framework, thereby improving overall strength. This research establishes a theoretical and experimental foundation for alkali-activated fly ash-phosphogypsum stabilization of expansive soils.