Network analyses of biological communities allow for identifying potential consequences of climate change on the resilience of ecosystems and their robustness to resist stressors. Using DNA metabarcoding datasets from a three-year-sampling (73 samples), we constructed the protistan plankton co-occurrence network of Lake Zurich, a model lake ecosystem subjected to climate change. Despite several documentations of dramatic lake warming in Lake Zurich, our study provides an unprecedented perspective by linking changes in biotic association patterns to climate stress. Water temperature belonged to the strongest environmental parameters splitting the data into two distinct seasonal networks (October–April; May–September). The expected ecological niche of phytoplankton, weakened through nutrient depletion because of permanent thermal stratification and through parasitic fungi, was occupied by the cyanobacterium Planktothrix rubescens and mixotrophic nanoflagellates. Instead of phytoplankton, bacteria and nanoflagellates were the main prey organisms associated with key predators (ciliates), which contrasts traditional views of biological associations in lake plankton. In a species extinction scenario, the warm season network emerged as more vulnerable than the cold season network, indicating a time-lagged effect of warmer winter temperatures on the communities. We conclude that climate stressors compromise lake ecosystem robustness and resilience through species replacement, richness differences, and succession as indicated by key network properties.