Unraveling how microbial co-occurrences respond to cyanobacterial blooms is central to our understanding of the stability of aquatic ecosystems. Here, we examined the effects of a Microcystis bloom on the inter-domain eukaryotic and two size-fractionated bacterial networks in a subtropical reservoir. Eukaryotes, especially protists, had a central role in microbial networks, followed by particle-attached (PA) bacteria and free-living (FL) bacteria. Eukaryotes had more negative correlations with PA bacteria than with FL bacteria. The environmental changes related to the Microcystis bloom (i.e., water temperature, pH, chlorophyll a, total carbon, total organic carbon and nitrite nitrogen) strongly affected eukaryotes and PA bacteria network as reflected by the dynamics of community composition in major modules. Importantly, the network complexity and stability significantly increased in the post-bloom periods, and eukaryotes (especially protists) enhanced the stability of the microbial network. Compared to keystone FL bacteria, eukaryotic and PA bacterial hubs mainly determined the network structure and key functional potentials (i.e., nitrogen cycling, carbon fixation and carbon degradation). Thus, some keystone eukaryotes and PA bacteria might be used as indicators of the structure and function stability of microbial communities in reservoir ecosystems. Our study highlights the importance of considering microbial cross-kingdom and multiple size-fractionation correlations in evaluating the effects of environmental disturbances on microbial networks.