Aerosol optical depth (AOD) is an essential metric for evaluating the atmospheric aerosol load and its impacts on climate, air quality, and public health. In this study, the AOD data from the Copernicus Atmosphere Monitoring Service (CAMS) were validated against ground-based measurements from the Aerosol Robotic Network (AERONET) throughout the Eastern Mediterranean, a region characterized by diverse aerosol types and sources. A comparative analysis was performed on 3-hourly CAMS AOD values at 550 nm against observations from 20 AERONET stations across Cyprus, Greece, Israel, Egypt, and Turkey from 2003 to 2021. The CAMS AOD data exhibited a good overall agreement with AERONET AOD data, demonstrated by a Pearson correlation coefficient of 0.77, a mean absolute error (MAE) of 0.08, and a root mean square error (RMSE) of 0.11. Nonetheless, spatial and temporal variations were observed in the CAMS AOD data performance, with site-specific correlation coefficients ranging from 0.57 to 0.85, the lowest correlations occurring in Egypt and the highest in Greece. An underestimation of CAMS AOD was noted at inland sites with high AOD levels, while a better agreement was observed at coastal sites with lower AOD levels. The diurnal variation analysis indicated improved CAMS reanalysis performance during the afternoon and evening hours. Seasonally, CAMS reanalysis showed better agreement with AERONET AODs in spring and autumn, with lower correlation coefficients noted in summer and winter. This study marks the first comprehensive validation of CAMS AOD performance in the Eastern Mediterranean, offering significant enhancements for regional air quality and climate modeling, and underscores the essential role of consistent validation in refining aerosol estimations within this complex and dynamic geographic setting.