More than 300,000 tonnes of brewer’s spent grain (BSG) is generated annually during beer production. This protein- and nutrient-rich by-product is mostly employed as an animal feedstuff. However, its marketability is compromised by its rapid deterioration owing to its high humidity and fermentable sugar content. Drying BSG can be achieved using the bio-energy generated from the anaerobic digestion of part of the BSG produced in the same brewery. We employed three types of strategies to enhance the biomethanation of BSG in mesophilic batch incubations. First, we co-digested BSG with peach flesh residues, juice residues, sewage sludge and pig slurry. Second, we supplemented BSG with chemical additives (carbon and energy sources) in order to biostimulate the methane-producing microbial communities. Finally, we used anaerobically acclimatised BSG to augment the initial microbial load in assays digesting BSG either alone or in co-digestion with sewage sludge. All co-substrates assayed were suitable to be fermented in combination with BSG, although methane production was highest for the mixtures with sewage sludge and pig slurry, with their high pH values and nutrient contents. Nine out of 14 combinations of stimulatory chemicals significantly enhanced BSG methanation compared with a non-supplemented control. Overall, bioaugmenting the anaerobic microbial consortia by using fermented BSG as an inoculum when co-digesting BSG with sewage sludge performed best in terms of methane yield.