Microorganisms underpin the health and function of coral reefs and are sensitive to environmental changes that directly affect ecosystem stability. This rapid and sensitive response of marine microorganisms to environmental perturbation can be exploited to provide robust indicators for reef monitoring. While opportunistic and potentially pathogenic microbial taxa persistently associate with degraded reefs (e.g. increased nutrient loads and macroalgae cover, coral bleaching/disease), we currently have a poor understanding of how changes in microbial function may translate to changes in reef health. This study provides a baseline of reef seawater and sediment microbial community function across observatory stations established at key inshore and offshore sites of the Great Barrier Reef. In partnership with the Australian Integrated Marine Observing System (IMOS), we collected extensive metagenomic and metatranscriptomic data alongside water chemistry and benthic cover measurements to identify changes in microbial activity in response to shifting environmental parameters across space and time. We successfully identified multi-omic molecular signatures of opportunistic microbial function/activity associated with nutrient enrichment in degraded inshore reefs. This knowledge is critical to develop microbial-based monitoring assays for rapid assessment of reef ecosystem health and to identify early warning signs of coral reef health deterioration.