Research into microbial fuel cells (MFCs) has reached the point where cubic metre-scale systems and stacks are being built and tested. Apart from performance enhancement through catalysis, materials and design, an important research area for industrial applicability is stack control, which can enhance MFCs stack power output. An MFC stack is controlled using a sampled-time digital control strategy, which has the advantage of intermittent operation with consequent power saving, and when used in a hybrid series stack connectivity, can avoid voltage reversals. A MFC stack comprising four tubular MFCs was operated hydraulically in series. Each MFC was connected to an independent controller and the stack was connected electrically in series, creating a hybrid-series connectivity. The voltage of each MFC in the stack was controlled such that the overall series stack voltage generated was algebraic sum (1.26 V) of the individual MFC voltages (0.32, 0.32, 0.32 and 0.3). The controllers were able to control the individual voltages to the point where 2.52 mA was drawn from the stack at a load of 499.9 Ω (delivering 3.18 mW). The controllers were able to reject the disturbances and perturbations caused by electrical loading, temperature and substrate concentration.