Microbial community structures are shaped by geochemical factors and their interactions with the lithosphere, hydrosphere, and atmosphere through the processes of chemical mobilisation and mineralisation. High-altitude wetlands and salt flats in the central Andes are characterised by pronounced physicochemical gradients and extreme climatic conditions, representing hotspots of microbial diversity. We here hypothesise about the existence of direct relationships between the local microbiology and the climate cyclicity variables based on meteorological and biogeochemical patterns that develop over a short time scale (five years). We have here analysed the interactions between hydrometeorological and biogeochemical variables and the microbial communities of the Salar de Huasco. These results were obtained by correlating 16S cDNA and DNA gene Illumina sequences with meteorological/satellite data collected both at monitoring stations and by remote sensing between the years 2015 and 2020. The precipitation levels and flooded areas (i.e., areas covered and/or saturated with permanent water) detected in the Salar de Huasco revealed a marked hydric cyclicity that correlated seasonally with intra-annual wet and dry seasons. Overall, at this site, wet periods occurred from December to April, and dry periods from May to November. Meteorological variables such as solar radiation, air temperature, relative humidity, wind speed, atmospheric pressure, and wind direction were well-defined, showing a potential association with the hydrogeology of the area, which is directly related to the wetlands' flooded areas. Finally, the microbial presence and potentially active microbial communities were determined through the sequencing of the 16S gene (DNA and cDNA, respectively), this were associated with climatic seasonality and spatially distributed physical and chemical heterogeneity. Other non-local inter-annual scale processes, such as El Niño-Southern Oscillation (ENSO) events, modify the physical and chemical context of the wetland, thus forming unique ecological niches in the Andean Mountains.