Membrane distillation (MD) has a high heat requirement. Integrating MD with thermophilic bioreactors could remedy this problem. A laboratory-scale thermophilic anaerobic granular sludge membrane distillation bioreactor (ThAGS-MDBR) was used to treat wastewater with a high organic loading rate (OLR). Waste heat from ThAGS was used directly for the MD process to reduce energy consumption. The result demonstrated that the ThAGS-MDBR system achieved a high-efficiency removal of chemical oxygen demand (more 99.5%) and NH4+-N (96.4%). Furthermore, the highest methane production from the proposed system was 332 mL/g CODremoved at OLR of 16 kg COD/m3/day. Specifically, an aggregate of densely packed diverse microbial communities in anaerobic granular sludge was the main mechanism for the enhancement of bioreactor tolerance with environmental changes. High-quality distillate water from ThAGS-MDBR was reclaimed in one step with total organic carbon less than 1.7 mg/L and electrical conductivity less than 120 μS/cm. Furthermore, the result of the DNA extraction kit recorded that Methanosaeta thermophila was a critical archaea for high COD removal and bioreactor stability.