The interactions of water, energy, and food, which are essential resources for human survival, livelihoods, production, and development, constitute a water–energy–food (WEF) nexus. Applying symbiosis theory, the economic, social, and natural factors were considered at the same time in the WEF system, and we conducted a micro-level investigation focusing on the stability, coordination, and sustainability of the symbiotic units (water, energy, and food), and external environment of the WEF system in 36 prefecture-level cities across three northeastern provinces of China. Finally, we analyzed the synergistic safety and coupling coordination degree of the WEF system by the combination of stability, coordination, and sustainability, attending to the coordination relationship and influences of the external environment. The results indicated that the synergistic safety of the WEF system in three northeastern provinces need to equally pay attention to the stability, coordination, and sustainability of the WEF system, since their weights were 0.32, 0.36 and 0.32, respectively. During 2010–2016, the synergistic safety indexes of the WEF system ranged between 0.40 and 0.60, which was a state of boundary safety. In the current study, the coupling coordination degree of the WEF system fluctuated around a value of 0.6, maintaining a primary coordination level; while in the future of 2021–2026, it will decline to 0.57–0.60, dropping to a weak coordinated level. The conclusion could provide effective information for decision-makers to take suitable measures for the security development of a WEF system.