Gypsum-bearing salt rock in the Cretaceous Guankou Formation is widely distributed in the southern suburbs of Chengdu and may undergo significant strength attenuation under water–rock interaction. Based on a 35-day immersion experiment, this study investigates the mechanical degradation, microstructural evolution, and engineering implications of gypsum rock. Laboratory mechanical tests, X-ray diffraction analysis, thin-section observations, and deterioration-index analysis were conducted to establish the relationship between time-dependent strength attenuation and microstructural damage. The results show that gypsum rock exhibits rapid strength and stiffness degradation after immersion. The uniaxial compressive strength (UCS) retention ratio decreased from 1.00 to 0.63 after 7 days and further to 0.26 after 35 days, while the elastic modulus retention ratio decreased to 0.33 after 35 days. The deterioration process can be divided into three stages: rapid softening, pore–fissure development, and structural fragmentation. Microscopically, gypsum dissolution, cement loss, pore enlargement, fissure propagation, and weakening of intercrystalline bonding progressively damage the rock fabric. Macroscopically, these processes are manifested as mass loss, surface dissolution, volume reduction, stiffness attenuation, strength reduction, and a brittle-to-plastic transition in failure mode. The results indicate that dry-state mechanical parameters may overestimate the stability of gypsum-bearing rock masses under groundwater disturbance. Water-degraded mechanical parameters, groundwater chemistry monitoring, drainage control, waterproofing, grouting reinforcement, and anti-corrosion measures should be considered in engineering construction in gypsum-bearing red-bed areas.