Current luminescence materials are abundantly available for visualization fields on a theoretical level, while the lack of luminescent intensity has largely hindered their practical application. Here, the substantial enhancement of the multimode luminescence is demonstrated including mechanoluminescence (ML), photoluminescence (PL), and X-ray excited optical luminescence (XEOL) for Mn2+ and Tb3+ in zinc calcium oxysulfide (CaZnOS) by increasing the concentration of oxygen vacancies (OVs). Through a comprehensive structure analysis, it is found that the CaZnOS lattice has a tolerance of 60% of Sr2+ with respect to Ca2+ in the methodology. The experimental characterizations verified that the lattice distortion of CaZnOS originating from Sr2+ incorporation can efficiently promote the elimination of oxygen elements and simultaneously produce more OVs in the matrix, which can effectively fortify the trapped electrons and ultimately promote stronger luminescence. The ML, PL, and XEOL achieve around two to six times’ enhancement after Sr2+ incorporation. The findings provide insight into mechanisms underlying the luminescence behavior change of phosphors after cation substitution and may have wide implications for the practical application of intrinsically defective phosphors.