Biorefinery wastewaters are often treated by means of anaerobic digestion to produce biogas. Alternatively, these wastewaters can be fermented, leading to the formation of carboxylates. Here, we investigated how lab-scale upflow anaerobic sludge blanket reactors could be shifted to fermentation by changing organic loading rate, hydraulic retention time, pH, and salinity. A strong increase in volatile fatty acid concentration up to 40 g COD L(-1) was achieved through increasing salinity above 30 mS cm(-1), as well as a decrease in methane production by more than 90%, which could not be obtained by adjusting the other parameters, thus, indicating a clear shift from methane to carboxylate production. Microbial community analysis revealed a shift in bacterial community to lower evenness and richness values, following the increased salinity and VFA concentration during the fermentation process. A selective enrichment of the hydrogenotrophic Methanomicrobiales took place upon the shift to fermentation, despite a severe decrease in methane production. Particle size distribution revealed a strong degranulation of the sludge in the reactor, related to the high salinity, which resulted in a wash-out of the biomass. This research shows that salinity is a key parameter enabling a shift from methane to carboxylate production in a stable fermentation process.