Wastewater treatment plants (WWTPs) are municipal facilities where water and energy are highly interconnected. They remove pollutants from the sewage while large amounts of energy are consumed with greenhouse gases emitted. Thus, energy neutrality potential (ENP) is a critical indicator to represent the conversion situation of water and energy in WWTPs. This study proposed a novel framework to evaluate the ENP through the combination of comprehensive water-energy efficiency (dimensionless) and energy self-sufficiency (%) of WWTPs. The efficiency of wastewater treatment was quantified and energy recovery potentials in terms of chemical and thermal energy were estimated. The framework was applied to 970 WWTP samples in Yangtze River Economic Belt region in China. To categorize the ENP levels, the critical value of comprehensive water-energy efficiency was 0.544, while that of energy self-sufficiency was 67.26%. The results can provide guidance for optimizing the energy efficiency and recovery of WWTPs to realize the neutrality. The framework could also be suitable for WWTPs in other regions worldwide.