Engineering structures in salt-affected desert regions of southern Xinjiang are highly vulnerable to environmental deterioration, while local aggregate scarcity further constrains conventional concrete production. To improve material sustainability and local resource utilization, a lightweight expanded polystyrene desert-sand concrete (EPS-DSC) was developed using EPS beads and DS as partial replacements. This study evaluates the mechanical properties and degradation behavior of EPS-DSC under non-corrosive exposure, sulfate attack, chloride-sulfate attack, and coupled wet-dry cycles. Results show that DS at an optimal mass replacement ratio of approximately 35% improves both workability and strength, whereas excessive DS leads to deterioration due to increased paste demand. The incorporation of 5-10% EPS reduces compressive strength but enhances crack resistance. Under Na2SO4 exposure, compressive strength of EPS-DSC increases with curing age and reaches a gain of approximately 53% at 28 days due to pore refinement, after which it stabilizes. Under coupled chloride-sulfate attack, strength exhibits a non-monotonic trend, peaking at around 75 days before declining due to crystallization-induced expansion and microcrack propagation. When wet-dry cycles are introduced, compressive strength decreases with increasing cycle number, exhibiting a three-stage pattern: initial stabilization, accelerated deterioration, and late-stage deceleration. Mechanistically, the synergistic effects of EPS-induced crack-bridging and DS-enhanced pore refinement effectively mitigate microstructural damage and delay strength degradation at early stages. However, long-term durability remains adversely affected by sulfate expansion. These findings provide guidance for the application of sustainable lightweight concrete in saline environments.