Estuaries are facing multiple stressors including warming, eutrophication, acidification, and hypoxia, yet the cumulative impacts of these stressors on estuarine microbial communities remain poorly resolved. Two core questions remain open: 1) Do individual stressors elicit distinct or convergent community responses?  2) How does environmental context modulate microbial sensitivity? We conducted ship-based incubation experiments with surface seawater from stations along the salinity gradient at the Yangtze River Estuary (YRE) and Pearl River Estuary (PRE) during spring and summer, exposing microbial communities to eutrophication, CO₂-driven acidification (ΔpH ≈ −0.4 and −0.6), and deoxygenation (~4 and ~2 mg/L dissolved oxygen) for 24 hours. Microbial communities were characterized using 16S rRNA amplicon sequencing, metagenomics, and metatranscriptomics. In all treatments, the short-term stress did not trigger fundamental reorganization of community structures. Samples clustered primarily by stations rather than experimental treatments. Nevertheless, deoxygenation emerged as a key driver reconstructing microbial communities (most pronounced in summer PRE). Deoxygenation induced significant shifts in co-occurrence network topology, and elevated prokaryotic taxonomic turnover. We reconstructed 714 metagenome-assembled genomes (MAGs) from metagenomic data. Focusing on the summer PRE, we uncovered two divergent ecological strategies among deoxygenation-responsive prokaryotic lineages: taxa that increased in relative abundance under deoxygenation possessed smaller genomes with enriched genetic and environmental information processing pathways, whereas taxa that decreased harbored larger genomes with broader metabolic repertoires. Metatranscriptomic analysis of the summer PRE community revealed that deoxygenation (H2, ~2 mg/L) triggered significant transcriptional reprogramming, including the down-regulation of ABC transporters and the up-regulation of two-component systems, secretion systems and biofilm formation. In contrast, during spring, fewer taxa showed significant relative abundance changes in response to deoxygenation. The divergent genomic strategies uncovered in this study reveal that microbial responses to deoxygenation are fundamentally shaped by evolutionary trade-offs between metabolic versatility and stress defense capacity. Overall, our findings demonstrate that environmental stressors may elicit highly distinct rather than convergent responses in estuarine microbial communities, with deoxygenation acting as the dominant driver of short-term shifts in community composition and functional potential. Environmental context further modulates response sensitivity: seasonal warming substantially amplifies the ecological impacts of deoxygenation. These results provide a trait-based mechanistic framework for predicting estuarine microbiome trajectories under ongoing coastal deoxygenation and future climate change.