The capacity of marine ecosystems to adapt to environmental stress is inherently linked to the functionality of their microbiomes. Yet, microorganisms are rarely the focus of conservation policies, and establishing quantitative microbial sensitivity thresholds remains challenging. Here, we present a framework to quantitatively assess absolute microbial community and amplicon sequence variant (ASV)-level responses to environmental contamination by integrating 16S rRNA gene amplicon sequencing with ecotoxicology concentration-response modelling. Microbial sensitivity thresholds were estimated for significant indicator ASVs and combined into a Prokaryotic Sensitivity Distribution, from which novel microbiome Hazard Concentrations (mHCx) were derived, where x percent of the community were affected. The framework was applied to seawater microbiomes across a disturbance gradient, each exposed to experimental copper contamination. We identified increased copper sensitivities in microbiomes from ecosystems of high ecological value compared to those of highly disturbed sites. The proposed framework represents significant progress in quantitatively assessing contaminant effects on microbial communities and supports their inclusion in environmental risk assessments.