To date, it remains unclear how anthropogenic perturbations influence the dynamics of microbial communities, what general patterns arise in response to disturbance, and whether it is possible to predict them. Here, we suggest the use of microbial mats as a model of study to reveal patterns that can illuminate the ecological processes underlying microbial dynamics in response to stress. We traced the responses to anthropogenic perturbation caused by water depletion in microbial mats from Cuatro Cienegas Basin (CCB), Mexico, by using a time-series spatially resolved analysis in a novel combination of three computational approaches. First, we implemented MEBS (Multi-genomic Entropy-Based Score) to evaluate the dynamics of major biogeochemical cycles across spatio-temporal scales with a single informative value. Second, we used robust Time Series-Ecological Networks (TS-ENs) to evaluate the total percentage of interactions at different taxonomic levels. Lastly, we utilized network motifs to characterize specific interaction patterns. Our results indicate that microbial mats from CCB contain an enormous taxonomic diversity with at least 100 phyla, mainly represented by members of the rare biosphere (RB). Statistical ecological analyses point out a clear involvement of anaerobic guilds related to sulfur and methane cycles during wet versus dry conditions, where we find an increase in fungi, photosynthetic, and halotolerant taxa. TS-ENs indicate that in wet conditions, there was an equilibrium between cooperation and competition (positive and negative relationships, respectively), while under dry conditions there is an over-representation of negative relationships. Furthermore, most of the keystone taxa of the TS-ENs at family level are members of the RB and the microbial mat core highlighting their crucial role within the community. Our results indicate that microbial mats are more robust to perturbation due to redundant functions that are likely shared among community members in the highly connected TS-ENs with density values close to one (≈0.9). Finally, we provide evidence that suggests that a large taxonomic diversity where all community members interact with each other (low modularity), the presence of permanent of low-abundant taxa, and an increase in competition can be potential buffers against environmental disturbance in microbial mats.