The automation of biodigesters using programmable logic controllers (PLCs) is well established, yet mixing schedules are configured empirically, regardless of substrate characteristics. This study proposes a Substrate-Driven PLC Control (SD-PLC) methodology for fixed-dome biodigesters, in which every timing setpoint is derived from a measured substrate property: the homogenization pulse from the rheological mixing time (Metzner–Otto regime), the maintenance interval from a stratification and a substrate–biomass contact criterion, the duty-cycle ceiling from a net energy balance, and a safety gate from acid–base behavior (pH/EC). The methodology is instantiated on a 13.86 m3 fixed-dome biodigester in the Chillón Valley (Lima, Peru), co-digesting organic waste and guinea pig manure (30:70; theoretical methane potential 371 mL CH4 g−1 VS; field conversion ≈ 21%). The impeller operates in the transitional regime (–), the homogenization pulse is ≈22 min, and the reconciled duty cycle () remains a factor of four below the energy ceiling (). An influence × feasibility matrix identifies a low-cost sensor set (pH, electrical conductivity, temperature, level) that gates mixing. A reduced COD-based dynamic model shows that, under acid shock, continuous mixing suppresses methanogenesis through shear while the absence of mixing fails through contact deficit, so that only the stability-first strategy preserves the process. The principal contribution is the methodology itself—a reproducible mapping from substrate characterization to PLC timing design—rather than the hardware.