Mechanoluminescence (ML) in a CaAl2Si2O8:Eu2+ phosphor was greatly enhanced by partial Sr2+ substitution for Ca2+; ML intensity reached a maximum at Sr2+ content of 40 mol %. Moreover, ML was not observed at Sr2+ content of 80 mol % or higher. To investigate the relationship between ML and the crystal structure, Rietveld refinement of the crystal structures was performed, the results of which suggest that the observed ML enhancement and quenching phenomenon were associated with changes in the crystal lattice and crystal symmetry. Furthermore, the effects of partial Sr2+ substitution on the structure and photoluminescence characteristics were also investigated, and the emission peak was blueshifted from 428 to 403 nm due to the decrease in the crystal field intensity around Eu2+. Based on electroluminescence measurements and the structural properties of the material, a possible mechanism for the enhancement in ML intensity is proposed.