Two analogues of rofecoxib, 2-Pyr-ROF and 2-Pip-ROF, were designed according to the strategy of heterocyclic ring enlargement and facilely synthesized in a facile manner by Knoevenagel reactions. The first compound, 2-Pyr-ROF, had low quantum yields (QY) of 3.0% in the solid states. After replacing the pyrrolidinyl with piperidinyl, the resulting 2-Pip-ROF had a significantly increased QY, with a value of 28%. The root-mean-square deviation (RMSD) values between S0 and S1 of 2-Pyr-ROF and 2-Pip-ROF in tetrahydrofuran were 0.51, 0.35 Å, respectively. As compared with 2-Pyr-ROF, compound 2-Pip-ROF exhibits a smaller RMSD, which indicates a lower non-radiative transition rate. A single-crystal X-ray diffraction study and Hirshfeld surfaces analysis revealed that 2-Pip-ROF had a more nonplanar molecule structure and a weaker π-π interaction, which might result in a higher fluorescence intensity and QY. Owing to its better aggregation-induced emission (AIE) behavior, compound 2-Pip-ROF showed more multi-functional applications, including mechanochromism, acidochromism, and lipid droplets imaging ability. These results imply that the strategy of heterocyclic ring enlargement provides a new paradigm for the design of new luminogens with AIE properties.