Algal photosynthesis plays a key role in the removal mechanisms of waste stabilization ponds (WSPs), which is indicated in the variations of three parameters, dissolved oxygen, pH, and chlorophyll a. These variations can be considerably affected by extreme climatic conditions at high altitude. To investigate these effects, three sampling campaigns were conducted in a high-altitude WSP in Cuenca (Ecuador). From the collected data, the first application of structure equation modeling (SEM) on a pond system was fitted to analyze the influence of high-altitude characteristics on pond performance, especially on the three indicators. Noticeably, air temperature appeared as the highest influencing factors as low temperature at high altitude can greatly decrease the growth rate of microorganisms. Strong wind and large diurnal variations of temperature, 7–20 °C, enhanced flow efficiency by improving mixing inside the ponds. Intense solar radiation brought both advantages and disadvantages as it boosted oxygen level during the day but promoted algal overgrowth causing oxygen depletion during the night. From these findings, the authors proposed insightful recommendations for future design, monitoring, and operation of high-altitude WSPs. Moreover, we also recommended SEM to pond engineers as an effective tool for better simulation of such complex systems like WSPs.