This study aims to determine the seasonal variability in the performance of a medium size population wastewater treatment plant (WWTP) in Bolivia. The semi-arid area where the WWTP is located is characterized as agricultural land, with an annual rainfall of 500 mm and a mean temperature of 17 °C. The WWTP is built up of five modules, each one comprising two treatment trains composed of an upflow anaerobic sludge blanket (UASB) reactor and horizontal gravel filter. The performance of the full process has been determined based on water quantity and quality. Seven monitoring campaigns of chemical and physical wastewater characteristics were performed from March to December 2017. The measured effluent showed average removal efficiencies of 83 ± 8% and 37 ± 60% for total chemical oxygen demand (COD) and total suspended solids (TSS), respectively. The treatment system has proven to be efficient to remove organic matter and TSS, despite the occurrence of high COD and total solids (TS) influent concentrations, the accumulation of solids at all the processes and the variability of flow and temperature inside the UASB reactors. In order to improve further this efficiency, it is recommended to implement a primary sedimentation unit as a pretreatment for the UASB system that would help to homogenize both the flow and the quality of the influent.