Dust storms represent a major environmental challenge in the Middle East. The southwest part of Iran is highly affected by dust events transported from neighboring desert regions, mostly from the Iraqi plains and Saudi Arabia, as well as from local dust storms. This study analyzes the spatio-temporal distribution of dust days at five meteorological stations located in southwestern Iran covering a period of 22 years (from 1997 to 2018). Dust codes (06, 07, 30 to 35) from meteorological observations are analyzed at each station, indicating that 84% of the dust events are not of local origin. The average number of dust days maximizes in June and July (188 and 193, respectively), while the dust activity weakens after August. The dust events exhibit large inter-annual variability, with statistically significant increasing trends in all of five stations. Spatial distributions of the aerosol optical depth (AOD), dust loading, and surface dust concentrations from a moderate resolution imaging spectroradiometer (MODIS) and Modern-Era Retrospective analysis for Research and Applications (MERRA-2) retrievals reveal high dust accumulation over southwest Iran and surrounding regions. Furthermore, the spatial distribution of the (MODIS)-AOD trend (%) over southwest Iran indicates a large spatial heterogeneity during 2000–2018 with trends ranging mostly between −9% and 9% (not statistically significant). 2009 was the most active dust year, followed by 2011 and 2008, due to prolonged drought conditions in the fertile crescent and the enhanced dust emissions in the Iraqi plains during this period. In these years, the AOD was much higher than the 19-year average (2000 to 2018), while July 2009 was the dustiest month with about 25–30 dust days in each station. The years with highest dust activity were associated with less precipitation, negative anomalies of the vegetation health index (VHI) and normalized difference vegetation index (NDVI) over the Iraqi plains and southwest Iran, and favorable meteorological dynamics triggering stronger winds.