Possible deterioration of a rock’s structure and mechanical properties due to chemical reactions between the host rock, formation water, and CO2 requires due attention. In this study, cylindrical sandstone specimens obtained from the Hanna Formation, Wyoming, were prepared under three treatment conditions: dry, submerged in water, and treated with water + CO2 for one week at a pressure of 5 MPa and room temperature. Specimens were subjected to three effective confining pressures of 5, 15, and 25 MPa. The mechanical test results show that water + CO2 treatment, on average, decreases the peak strength and elastic modulus of the specimens by 36% and 20%, respectively, compared to dry specimens. For all three effective confining pressures, the dry specimens exhibited higher compressive strengths, larger Young’s moduli, and more brittle behavior. CO2-treated specimens showed significantly lower calcite contents.