Understanding the development of water environmental regulations over time and its response to external stress is crucial to enhance its performance, but there are few studies on it. This study aims to unfold the evolution of water environmental regulations in Chile and its response to changing water resources management, socio-economic, climate, and environmental conditions from 1900 to 2019. Content analysis was used to code the water environmental regulations, whereas trend analysis was carried out to identify the development stages, and both qualitative and quantitative co-evolutionary approaches were used to analyze the response of water environmental regulations to external changes. Results show that the development of water environmental regulations experienced the following four stages: the pre-development (1900-1980), slow development (1981-1993), development (1994-2009), and fast development (2010-2019). The development of water environmental regulations seriously lagged from water resources management and linearly responded to economic development and population growth. However, it presented a weak response to climate change and made limited impact on environmental degradation. Development of water environment regulations should be integrated and synchronized with water resources management in future.