The objective of the study presented in this paper is to investigate determinants of resilience in water infrastructure systems in developing countries using the case study of the 2015 Nepalese Earthquake. Because of differences in social, economic, technological, and political contexts, the characteristics of resilient systems in developing countries are different from those of the developed countries. Unfortunately, however, the understanding of various factors and phenomena influencing infrastructure resilience in developing countries is rather limited. To address this knowledge gap, this study investigated the water infrastructure of the Kathmandu Valley in the 2015 Nepalese earthquake through the use of a systems approach. The data collected from different sources ranging from agency interviews to postdisaster assessment reports were analyzed using a system resilience framework and qualitative information analysis using powerful, robust software. The results of the analysis then were summarized to capture various factors and their interactions influencing the resilience of the water system. The analysis highlighted various phenomena, such as scarcity-induced negligence, human-infrastructure coupling, emergence of new dependencies, and adaptive capacity developed under chronic stressors, that led to the resilience performance of the water system in the Kathmandu Valley. The results highlight the importance of better understanding of human-infrastructure coupling, adaptive capacity, and systems transformation under chronic stressors for resilience analysis of infrastructure systems. The findings also have important implications for policymakers in developing and developed countries by identifying strategies that can bolster the resilience of infrastructure systems.