A novel system (Oregon State University High Solids Reactor; OSU-HSR) was designed and constructed for enzymatic hydrolysis at ultrahigh solids content (40%) by promoting better mixing using low energy consumption in a horizontal reactor with a new impeller design and a controllable feeding unit. System performance was evaluated using separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) methodologies. Using the dilute acid pretreated wheat straw as the substrate in the OSU-HSR system, the highest glucose (219.7 g/L) and ethanol (127.1 g/L) concentrations were achieved with the use of the SHF method while the highest ethanol concentration using SSF method was 134.5 g/L. The SSF method increased the return on investment to 12.21% with an estimated global warming potential of 54.5 g CO2 eq/MJ Ethanol. The OSU-HSR successfully provided effective mixing and different fed-batch schemes, and can be used for efficient biochemical conversion of lignocellulosic biomass into bio-chemicals and biofuels.