Mercury (Hg) is a toxic metal that can be released from natural and anthropogenic processes. Gaseous elemental Hg is the main form of Hg in the atmosphere with a long residence time, allowing its long-range transport and deposition at a global scale. The deposited Hg can be transformed into methylmercuy (MeHg), which bioaccumulates and biomagnifies in aquatic ecosystems and is a known developmental neurotoxin to humans. Chronic exposure in pregnant women via fish consumption, even at the modest levels, can impact intellectual development in infants, which is considered as a global environmental health issue. To protect human health and the environment, the Minamata Convention on Mercury, a legally binding international treaty, entered into force in 2017 to reduce anthropogenic emissions and releases of Hg and Hg compounds. With the enforcement of the Convention, anthropogenic Hg emissions and releases are projected to decrease in the foreseeable future, but the recovery of the ecosystem and mitigation of health impact from Hg pollution are expected to lag behind. In this paper, we provide a critical review on the processes affecting when and to which extent Hg-affected ecosystems will recover under the Minamata Convention in the context of climate change and associated human health benefit. Our review is organized around seven major scientific questions. These seven questions covered historical Hg change in the ecosystem, major factors and processes, and future assessment. The impact of implementation of Minamata Convention and climate change on Hg emission, atmospheric transportation and deposition, biota accumulation, and human exposure should be comprehensively evaluated. The Hg stable isotope tool and process-based integrated global model should be integrated together, which also should consider future global social-economic pathways and mitigation options. We hope that the knowledge gaps and potential tools identified will assist the understanding of global biogeochemical cycling of Hg, inform policy-making on mitigation and community adaptation, and support the effectiveness evaluation and future improvement of the Minamata Convention on Mercury.