Due to their tunable acidity, shape selectivity, and excellent stability, zeolites are of great importance as solid acid materials in industrial catalysis. Tuning the properties of the acid sites in zeolites allows for the rational design and fabrication of catalysts for target reactions. Dimethyl ether (DME) carbonylation, a critical chain-growth reaction for C1 resource utilization, is selectively catalyzed by the Brønsted acid sites within the eight-membered rings (8-MRs) of mordenite (MOR). It is anticipated that strengthening the Brønsted acidity—particularly in 8-MRs—will improve the catalytic performance of MOR. In this work, density functional theory (DFT) calculations are first employed and the results used to design a modified MOR with stannum (Sn) and to predict the corresponding changes in acidity. Guided by the theoretical studies, a series of Sn-modified MOR are synthesized via a defect-engineering and subsequent heteroatom-substitution strategy. After partial desilication, isolated tetrahedral Sn species in an open configuration are successfully synthesized for the first time, within which tetrahedrally coordinated Al sites are preserved. An acidic characterization is used to confirm that the acidity of the Brønsted acid sites is enhanced by the introduction of the Sn species; as a result, the sample exhibits excellent activity in DME carbonylation reaction. Kinetic and DFT studies reveal that this strengthened acidity facilitates the adsorption of DME and reduces the activation barriers of DME dissociation and acetyl formation, accounting for the improved activity. The work demonstrates mechanistic insights into the promoting effects of strong acidity on DME carbonylation and offers a promising strategy to precisely control the acidic strength of zeolites.