Chicken manure can be regarded as a valuable resource for energy recovery in rural areas. In this context, this study evaluated the co-digestion of chicken manure and wheat straw in leach bed reactors (LBRs). Among several parameters that can affect the process performance, the substrate-to-inoculum ratio (S/I), the proportion of chicken manure (CM%) in the substrate mixture, and the total solid content (TS) were optimized to improve the methane yield and the process stability. The increase of S/I to 2.38 resulted in higher methane productivity although higher volatile fatty acids concentrations were registered. The overall process efficiency was strongly affected by CM% increase resulting in propionic acid accumulation and lower methane production. The simultaneous increase of S/I and TS while keeping the CM % at 55% in the substrate mixture not only resulted in a delay in the methanogenesis establishment but also compromised the hydrolysis step. Regardless of the start-up conditions, LBRs were able to recover from acidification although potentially inhibiting ammonia concentrations were registered, showing the versatility of LBRs to treat substrates with high ammonia content.