There is a recognized need for mineralizing aquaculture-derived sludge in aquaponics systems in order to reduce waste production. Many recent studies of aquacultural waste treatment have focused only the production of biogas as opposed to the potential for mineralization of nutrient-rich sludge. Upflow anaerobic sludge blanket (UASB) reactors provide one possible solution for breaking down sludge into bioavailable nutrients that can subsequently be delivered to plants. As such, this study examines the mineralization performance of sequential UASB reactors that are designed with an expanded granular sludge bed (EGSB) and compared to standard aerobic and anaerobic batch reactors. Results of our experiments demonstrate that only chemical oxygen demand reduction is significantly different. An unexpected drop in pH of one of the three reactor systems revealed that a pH below 6 was able to significantly increase the mineralization and mobilization of nutrients. Approximately 25% of phosphorus, potassium, and calcium could also be recovered from the sludge under lower pH conditions, as compared to the mineralization performance of standard UASB reactors running at a higher pH. However, the opposite effect was observed with respect to organic sludge reduction, where diminished performance was observed in the low-pH reactor. The current study implies that anaerobic reactors operating at low pH can potentially contribute towards improved nutrient recovery in multi-loop aquaponics systems and reduction of additive agents for pH control of the hydroponic subsystem.