The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2) provides data at 0.5° × 0.625° resolution covering a period from 1 January 1980 to the present. Natural and anthropogenic aerosols are simulated in MERRA-2, considering the Goddard chemistry, aerosol, radiation, and transport model. This model simulates the sources, sinks, and chemistry of mixed aerosol tracers: dust, sea salt, hydrophobic and hydrophilic black carbon and organic carbon, and sulfate. MERRA-2 aerosol reanalysis is a pioneering tool for investigating air quality issues, noteworthy for its global coverage and its distinction of aerosol speciation expressed in the form of aerosol optical depth (AOD). The aim of this work was to use the MERRA-2 reanalysis to study urban air pollution at a national scale by analyzing the AOD. AOD trends were evaluated for a 30-year period (1987–2017) over five Italian cities (Milan, Rome, Cagliari, Taranto, and Palermo) in order to investigate the impacts of urbanization, industrialization, air quality regulations, and regional transport on urban aerosol load. AOD evolution predicted by the MERRA-2 model in the period 2002–2017 showed a generalized decreasing trend over the selected cities. The anthropogenic signature on total AOD was between 50% and 80%, with the largest contribution deriving from sulfate.