Different inoculum sources and acclimatization methods result in different substrate adaptation and biodegradability. To increase straw degradation rate, shorten the digester start-up time, and enhance the biogas production, we domesticated anaerobic sludge by adding microcrystalline cellulose (MCC). During acclimatization, the start-up strategies and reactor performance were investigated to analyze changes in feedstock adaption, biodegradability, and methanogen activity. The effect of the domesticated inoculum was evaluated by testing batch un-pretreated corn stover with a dewatered sludge (DS)-domesticated inoculum as a control. The results showed that (1) using MCC as a substrate rapidly improved microorganism biodegradability and adaptation. (2) MCC as domesticated substrate has relatively stable system and high mass conversion, but with low buffer capacity. (3) Macro- and micronutrients should be added for improving the activity of methanogenic and system's buffer capacity. (4) Using the domesticated inoculums and batch tests to anaerobically digest untreated corn stover yielded rapid biogas production of 292 mL, with an early peak value on the first day. The results indicated that cultivating directional inoculum can efficiently and quickly start-up digester. These investigated results to promote anaerobic digestion of straw for producing biogas speed up the transformation of achievements of biomass solid waste utilization have a positive promoting significance.