Fish consumption is a major route of human exposure to mercury (Hg), yet limited understanding of how anthropogenic activities drive geographic variations in fish Hg worldwide hinders effective Hg pollution management. Here we characterized global geographic variations in total Hg (THg) and methylmercury (MeHg), compared THg and MeHg levels between the United States and China, and used a structural equation model to link the geographic variability of MeHg in fish to human activities. Despite previously reported higher Hg emissions in China, Chinese fish have lower THg and MeHg levels than fish in the United States owing to a lower trophic magnification slope, shortened food chains and shorter fish lifespans. The structural equation model revealed strong impacts of human activities on MeHg levels in fish. In the future, China may face elevated MeHg levels in fish with the ongoing recovery of food web ecology, highlighting the importance of local policies.