Land subsidence in the Yellow River Floodplain, approaching 60 mm/year, is severely exacerbated by annual groundwater oscillations of 3 to 8 m. Conventional hydro-mechanical models, which primarily rely on effective stress principles, often struggle to fully capture the moisture-induced structural degradation of calcareous cemented soils under such hydraulic disturbances. To address this theoretical gap, we conducted a multifactor orthogonal triaxial experiment to quantitatively decouple the macroscopic factors governing the hydro-mechanical degradation. The results reveal that moisture content acts as the absolute dominant driver, accounting for 81.65% of the variance in macroscopic shear strength variance and completely overwhelming the mechanical advantages provided by initial compaction. A generalized dual-path water-sensitive damage model was explicitly derived, mathematically uncovering a fundamental asynchronous degradation mechanism. Cohesion exhibits an inward-concave, brittle fracture trajectory, which is macroscopically inferred to be associated with the water-induced softening of calcareous bonds (phase-transition parameter 0.81, maximum allocation 75.1%). Conversely, the internal friction angle demonstrates an outward-convex, hysteretic decline (parameter 1.59), maintaining structural interlocking until severe water-film lubrication occurs. By decoupling highly state-dependent initial strength parameters from invariant degradation operators, the modified Mohr–Coulomb model achieved exceptional forward blind-prediction accuracy. Validations across distinct initial skeletal structures constrained relative prediction errors strictly between −19.3% and +13.7% without any subjective parameter recalibration. The quantified extreme vulnerability theoretically proves that minor water infiltration can instantly eradicate over 75% of cohesive strength, necessitating a paradigm shift from shallow mechanical compaction to stringent waterproofing in regional engineering practices.