A novel strategy for acclimation to ammonia stress was implemented by stimulating a high ammonia-ammonium-pH environment in a high-solid anaerobic digestion (AD) system in this study. Three semi-continuously stirred anaerobic reactors performed well over the whole study period under mesophilic conditions, especially in experimental group (R-2) when accommodated from acclimation period which the maximum total ammonia nitrogen (TAN) and free ammonia nitrogen (FAN) increased to 4921 and 2996 mg/L, respectively. Moreover, when it accommodated the high ammonia-ammonium-pH system, the daily biogas production and methane content were similar to those in R-1 (the blank control to R-2), but the hydrogen sulfide (H2S) content lower than the blank control. Moreover, mechanistic studies showed that high ammonia stress enhanced the activity of coenzyme F-420. The results of real-time fluorescent quantitative polymerase chain reaction (PCR) showed that ammonia stress decreased the abundance of sulfate-reducing bacteria and increased the abundance of methane-producing archaea.