This study assesses the aerosol optical depth (AOD) from historical simulations (2003–2014) and future climate scenarios (2015–2100) of the Coupled Model Intercomparison Project Phase 6 (CMIP6) over the Middle East and North Africa (MENA) region. Multi-model mean (MME) AOD statistics are generated as the average of those from the five best-performing CMIP6 models, which reproduce observational climate statistics. These models were selected based on the validation of various climate metrics, including strong pattern correlations with observations (>0.8). The resulting MME reproduces the observed AOD seasonal cycle well. The observed positive trends (summer and annual) over the Arabian Peninsula (AP) and negative trends (winter) over North Africa are well captured by MME, as regional meteorological drivers associated with observed AOD trends, with few discrepancies. Crucially, the MME fails to capture the AOD trends over North West Africa (NWA). For MENA and NWA regions, two high-emission scenarios, SSP370 and SSP585, project a continuous rise in the annual mean AOD until the end of the century. In contrast, the low-emission scenarios, SSP126 and SSP245, project a decreasing AOD trend. Interestingly, the projected future AOD area-averaged over the AP region varies significantly across all four scenarios in time. Notably, a substantial decrease of about 8–10% in the AOD is projected by the SSP126, SSP245, and SSP585 scenarios at the end of the century (2080–2100) relative to the current period. This projected decrease in annual-mean AOD, including the frequency of extreme AOD years under SSP585, is potentially associated with a concurrent increase in annual-mean rainfall over the AP.