Predictive modeling of CO2 storage sites requires a detailed understanding of physico-chemical processes and scale-up challenges. Dramatic injectivity decline may occur due to salt precipitation pore clogging in high-salinity aquifers during subsurface CO2 injection. This study aims to elucidate the impact of CO2-induced salt crystallization in the porous medium on the geomechanical properties of reservoir sandstones. As the impact of salt precipitation cannot be isolated from the precursor interactions with CO2 and acidified brine, we present a comprehensive review and discuss CO2 chemo-mechanical interactions with sandstones. Laboratory geochemical CO2–brine–rock interactions at elevated pressures and temperatures were conducted on two sandstone sets with contrasting petrophysical qualities. Interaction paths comprised treatment with (a) CO2-acidified brine and (b) supercritical injection until brine dry-out, salt crystallization, and growth. Afterward, the core samples were tested in a triaxial apparatus at varying stresses and temperatures. The elastic moduli of intact, CO2-acidified brine treated, and salt-affected sandstones were juxtaposed to elucidate the geochemical–geomechanical-coupled impacts and identify the extent of crystallization damages. The salt-affected sandstones showed a maximum of 50% reduction in Young’s and shear moduli and twice an increase in Poisson’s ratio compared to intact condition. The deterioration was notably higher for the tighter reservoir sandstones, with higher initial stiffness and lower porosity–permeability. We propose two pore- and grain-scale mechanisms to explain how salt crystallization contributes to stress localization and mechanical damage. The results highlight the potential integrity risk imposed by salt crystallization in (hyper)saline aquifers besides injectivity, signaling mechanical failure exacerbated by pressure buildup.