Waste containing explosive chemicals are hazardous to the environment. We suggested and implemented a hybrid approach for the destruction of nitrocellulose-containing sewage sludge (NCS) from a real chemical industrial complex. Combining chemical alkaline hydrolysis and mesophilic anaerobic digestion in a up-flow anaerobic sludge blanket (UASB) reactor allowed us to successfully achieve the balance between the environmental safety and economic efficiency of the stages of the treatment. After the alkaline treatment of waste at 50 °C with 1.5 M KOH, the solid residue contained mostly just sand and no nitrocellulose (NC). The liquid phase accumulated 2869 ± 24 mg N-NO2−/L and 1698 ± 51 mg N-NO3−/L. Bioconversion of the liquid phase neutralized with acetic acid and diluted with water by a factor of 50 in a 1 L UASB reactor ensured 99% efficiency of extracting N(NO2− + NO3−) and chemical oxygen demand (COD). Further, biogas with high methane content (>70%) was obtained. The establishment of the operational regime in the UASB reactor was achieved in two stages. The suggested hybrid approach to denitrification and methanogenesis is aimed at implementing the sustainable development concept in industrial chemical cycles. The results of this study are significant for researchers and technologists interested in developing hybrid processes for waste treatment that involve chemical catalysis as the first stage.