Dryland soil salinization strongly affects soil properties, with severe consequences for regional ecology, agriculture and the aeolian dust dynamics. Given its climate-sensitivity it forms a serious environmental hazard, and to cope with this challenge during current global warming it needs to be better understood. The Bajestan Playa in the strongly salinization-affected Iranian drylands hosts several protected areas and forms an important regional dust source. Hence, soil salinization in this region affects local and regional ecosystems and societies, but was not systematically studied yet. Using an unprecedented comprehensive approach we systematically monitored regional soil salinity 1992–2021 using remote sensing as well as on-site field and laboratory measurements, and linked these with regional and global climatic data to understand (i) the spatio-temporal soil salinity dynamics, (ii) the impact of regional and global climate changes, and (iii) the potential of our approach for further soil salinity studies. Our annual time resolution over three decades provided significantly deeper and unprecedented insights into soil salinization: Both regional annual precipitation and temperature control soil salinity, but the latter responds to precipitation with time lags of up to two years and to higher temperatures without any time lag. This probably reflects the transport time of leached soluble salts from their sources following humid years. No systematic soil salinity changes were observed within the playa basin, but outside the basin soil salinity systematically increased. Whereas regional precipitation did not show a systematic trend during the last decades, regional temperature increased and was mostly correlated with the increasing GLOTI, POL and TSA climatic indices. Hence, given ongoing global warming a further increase of regional soil salinization should be expected, with serious consequences for saline dust emissions, the regional protected areas and climate-related migrations. Altogether, our multi-disciplinary pioneer study demonstrates a high future application potential also for other salinity-affected drylands, forming a base to deal with the consequences of ongoing global climate change.