Reliability assessment of wastewater infrastructure is of utmost importance for sustaining wastewater operations amid various stressors, such as population growth and climate change, among other localized failures. While reliability assessment is applied widely at industrial scale, at present, there is no universally accepted tool to measure the reliability of wastewater infrastructure at a systemic scale. A novel approach was applied by integrating fault tree analysis (FTA) and event tree analysis (ETA) to assess the reliability of wastewater treatment systems and calculate their overall failure probability (FP). The results showed that the following factors had the highest contribution to FP in the existing system: infiltration (1), secondary clarifier (0.776), treated wastewater volume (0.75), influent wastewater quality (0.67), and population growth (0.6); eventually, the overall FP was calculated to be 0.5699. FTA and ETA were also used to predict failure probabilities for future events based on projected scenarios. In a 2035 scenario, the software results showed an increase in the overall FP from 0.5699 to 0.6025. On the other hand, in another scenario (2050), the overall system’s FP increased from 0.5699 to 0.8131. The proposed approach can be used as a decision-support framework for decision-makers and plant operators, and can be implemented in real-world cases.