A multivariable adaptive feedback control for highly uncertain continuous anaerobic digestion processes is proposed to regulate the volatile fatty acids (VFA) concentration, the strong ions concentrations, and the total and intermediate alkalinities. The multivariable control scheme includes a Luenberger observer to estimate both the unmeasured variables (i.e., VFA) and unknown microbial growth kinetics. The control approach is designed using an exponential Lyapunov function to resemble the typical exponential biological growth of the involved microbial consortia. Taking into account physicochemical equilibrium, alkalinities are represented as a function of the state variables. As a result, the control problem becomes a regulation problem on alkalinities, and in turn, a tracking control problem on the state variables, with two manipulated variables—the dilution rate and the feed rate of a strong alkali solution—while the state variables’ set-points are given as a function of pH. The implementation of this multivariable control scheme was experimentally tested and validated in a 0.982 m3 pilot plant treating agro-industrial wastewater, and demonstrated to be robust in the face of unknown microbial growth kinetics. Results showed the potential for practical application and optimization of industrial digesters.