Human intervention and climate change jointly influence the functions and dynamics of marine ecosystems. Studying the impacts of human and climate on ecosystem dynamics is challenging. Unlike experimental studies, research on natural systems is not amendable at the scale of time, space, and biology. With confounding factors well balanced for two adjacent subtropical estuaries except urbanized disturbances, we conducted ecosystem modelling using indirect reasoning by exclusion to quantify the relative impacts of human disruption on estuarine ecosystems under climate variability. One major finding of this study is that the human intervention tends to magnify species fluctuations, complicate the species interaction network, and enhance species interaction strength combined with disclosed downscaling climate effects (indexed as North Atlantic Oscillation and Atlantic Multi-decadal Oscillation) on estuarine hydrology and biological communities. In addition, functional groups appeared to respond more diversely to external forcing in company with human interventions. While human perturbation was shown to destabilize the estuarine ecosystems, making them vulnerable to environmental variability under climate change, buffering effects of species diversity and trophic interaction tend to underpin the ecosystem functions. The findings of this study contribute to the holistic assessment and strategic management of estuarine ecosystems subjected to human and natural disturbances in the face of climate change.