In disciplines related energy conversion, thermodynamics is the cornerstone for interpretation of process performance. It can provide the basis for the estimation of maximum convertible energy and spontaneity in novel, sustainable, anaerobic digestion processes. Here electrochemical thermodynamics is applied to the interpretation of glucose decomposition in anaerobic digestion of ethanol distillation residues (stillage) containing residual ethanol and ammonia. Under saturated conditions for biochemical mediators such as NAD+/NADH the microbial oxidations and reductions between hydrolytic fermentative bacteria, syntrophic acetogens and methanogens will always be close to or at the electrochemical equilibrium state through the mediator. The product distribution arising from the up-take of glucose is found to be sensitive to the electrochemical potential which is a measure of the thermodynamic driving force, ΔG and related to both ΔH and ΔS via the standard relationships. Glucose decomposition is strongly favorable and only weakly dependent on electrochemical potential in the range investigated. However the system showed overall ΔH <0, indicating the potential for significant exotherm but ΔS was also found to be less than zero, indicating that the forward reaction was not spontaneous. This work also finds that as the mole fraction of glucose, x, is increased up to x = 0.001, the thermodynamic driving force for hydrogenophilic methanogenesis is dramatically decreased whilst that for acetoclastic methanogenesis is increased, and the thermodynamic “inhibition” of beta oxidation of volatile fatty acids is reduced. This may be interpreted as the diversion of the metabolic pathway from the conventional route ‘glucose–acetate–CH4/CO2’ towards glucose–butrate–proprionate–acetate–CH4/CO2.