Treating wastewater is imperative for maintaining public health and sanitation as well as the natural environment. In the United States and developed countries around the globe, the activated sludge (AS) process has been paramount in effectively treating wastewater for over a century. However, high energy consumption due to required mechanical aeration of AS limits its potential as a sustainable process. The oxygenic photogranule (OPG) wastewater treatment process utilizes the photosynthetic ability of OPGs made possible by the symbiosis between heterotrophic AS and filamentous cyanobacteria and algae in dense, spherical biogranules. This research presents pilot operation of the OPG wastewater treatment process, supporting its scalability and effective nutrients removal. Four pilot OPG reactors were operated in sequencing batch reactor (SBR) mode with alternating light/dark cycles, achieving a maximum volume of 30 L (20-times scale-up factor) and maximum operation time of 152 days. Pilots A & B (Phase I) and Pilot D (Phase III) achieved soluble chemical oxygen demand (sCOD) removal efficiencies of 65%, 73%, and 81%, respectively, without any mechanical aeration. Pilot C (Phase II) employed a hybrid light/aeration system, attaining 83% sCOD removal with 12 hours of light (day) and aeration only (night). Observed biomass yield for OPG biomass was typically high (> 0.5 g VSS produced/g sCOD consumed compared to 0.3–0.5 for AS), signifying the production of energy-rich biomass. Very low observed yields (< 0.3) were observed during Pilot C operation, which may be advantageous for sludge reduction. Nitrogen removal was observed, but was inconsistent. The OPG system was able to treat real municipal wastewater with a wide range of F/M ratios (0.02–0.2 g sCOD/g VSS-d), and was robust to varying environmental conditions.