In this study, we have used the Terra satellite onboard of the Moderate Resolution Imaging Spectroradiometer (MODIS) to investigate the spatial and temporal relationship between aerosol optical depth (AOD) and cloud parameters namely, water vapor (WV), cloud optical depth (COD), cloud fraction (CF), cloud effective radius (CER), cloud top pressure (CTP), and cloud top temperature (CTT) based on 10 years (from January 2004 to December 2013) of dataset over six locations in South Africa (SA). The obtained results indicated seasonal variation in AOD, with high values during spring (September to November) and low values in winter (June to August) in all locations of study. In terms of temporal variation, AOD was lowest at Bloemfontein 0.06 ± 0.04 followed by Cape Town 0.08 ± 0.02, then Potchefstroom 0.09 ± 0.05, Pretoria and Skukuza had 0.11 ± 0.05 each and with the highest at Durban 0.13 ± 0.05. The mean Angstrom exponent (AE) values for each location showed a general prevalence of fine-mode particles which dominates the AOD for most parts of the year. A hybrid single particle Lagrangian integrated trajectory (HYSPLIT) model was used for trajectory analysis in order to determine the origin of airmasses and to understand the variability of AOD. We then studied the relationship between AOD, cloud parameters and precipitation over selected locations of SA so as to provide a better understanding of aerosol-cloud-precipitation interactions. All these correlations examined over six sites were observed to be depended on the large-scale meteorological variations.