Brewers' spent grain (BSG) is a low-value by-product of the brewing process, which is produced in large quantities every year. In this study, the lignocellulosic feedstock (solid BSG) was used to optimize fermentations with Cellulomonas uda. Under aerobic conditions, maximum cellulase activities of 0.98 nkat•mL −1 , maximum xylanase activities of 5.00 nkat•mL −1 and cell yields of 0.22 g Cells •g BSG −1 were achieved. Under anaerobic conditions, enzyme activities and cell yields were lower, but valuable liquid products (organic acids, ethanol) were produced with a yield of 0.41 g Prod •g BSG −1 . The growth phase of the organisms was monitored by measuring extracellular concentrations of two fluorophores pyridoxin (aerobic) and tryptophan (anaerobic) and by cell count. By combining reductive with anaerobic conditions, the ratio of ethanol to acetate was increased from 1.08 to 1.59 mol EtOH •mol Ac −1 . This ratio was further improved to 9.2 mol EtOH •mol Ac −1 by lowering the pH from 7.4 to 5.0 without decreasing the final ethanol concentration. A fermentation in a bioreactor with 15 w% BSG instead of 5 w% BSG quadrupled the acetate concentration, whilst ethanol was removed by gas stripping. This study provides various ideas for optimizing and monitoring fermentations with solid substrates, which can support feasibility and incorporation into holistic biorefining approaches in the future.