Identifying the bottleneck is the key to alerting and preventing unexpected failures of the nexus across water supply, power generation, and environment (WPE) systems. However, the bottleneck identification is challenged by the unclear concept of bottleneck as well as the difficulty of simulating complex emergent behaviors. Here, we develop a generic framework for identifying the bottleneck for the WPE nexus, which is defined as the subsystem that has the highest risk of leading to the failure of WPE nexus. First, the evolution of uncertainties of the state variables of WPE nexus is simulated by a generic stochastic dynamical system. Next, the propagation matrix, accumulation ratio (AR), and risk contribution ratio are defined as effective metrics and tools to identify the system bottleneck. Finally, the effects of human decisions and input stochasticity on the shifts of bottleneck are analyzed using sensitivity and scenario analysis. The WPE system in Hehuang Region, China, is selected as a case study. Results indicate that: (a) The effects of human decisions on ARs can be superimposed, suggesting a “superimposition method” for policy-making of Hehuang Region; (b) The subsystems can be classified as “endogenous” or “exogenous”, depending on the sources of accumulated uncertainties that are from local inputs, or inputs from the other subsystems; (c) There exist multiple bottlenecks at the same time that could shift from one subsystem to another, which complicates the prevention of the failures of WPE nexus. For the Hehuang Region, water and energy subsystems are more likely to be bottlenecks at the beginning stage, while society and environment subsystems are more likely to be bottlenecks at the steady stage. This study provides the first attempt to identify the bottleneck within the WPE nexus, which helps to provide realistic insights for preventing unexpected failures.