In this paper, a neuro-fuzzy control strategy composed by a neural observer and fuzzy supervisors for an anaerobic digestion process is proposed in order to maximize methane production. A nonlinear discrete-time recurrent high order neural observer (RHONO) is used to estimate biomass concentration and substrate degradation in a continuous stirred tank reactor. A Takagi-Sugeno supervisor controller based on the estimation of biomass, selects and applies the most adequate control action, allowing a smooth switching between open loop and closed loop. The control law calculates dilution rate and bicarbonate rate based on speed-gradient inverse optimal neural control. Finally, Takagi-Sugeno supervisors calculate reference trajectories for the system states, and gain scheduling for the dilution rate control law at different operating points of the process. The applicability of the proposed scheme is illustrated via simulations.