Enzymatic hydrolysis of hardwood substrates yields soluble sugars, which are a carbon source for producing ethanol and butanol. However, as the substrate and water are mixed, a viscous, heterogeneous slurry forms. The result is reduced mixing performance, mass transfer, and enzyme-substrate contact, all of which negatively affect sugar titers. In this study, enzymatic hydrolysis of a hardwood substrate at 20 wt% was conducted in a 10L stirred tank reactor. We investigated the dynamic changes in slurry behavior, as well as the interactions among mixer design/ operation and fed-batch strategies. The effects of the number and frequency of substrate additions, impeller configuration, and high and moderate agitation speeds were evaluated using torque measurements and in terms of glucan-to-glucose conversion. Fewer additions corresponds to batch operation and negatively impacted solids distribution, accurate torque readings, and glucan conversion. However, as the number of additions incrementally increased, glucan conversion increased, torque readings captured the resistance of the fluid to flow, and the solids distribution within the reactor improved. Moderate agitation speeds of 60 revolutions per minute (rpm), combined with smaller and more frequent fiber additions, led to increased glucan conversion and less torque resistance compared to similar experiments conducted at high rotational speeds (150 rpm), and the use of different impeller sizes and configurations impacted the distribution of the slurry. This work illustrates that the implementation of different fed-batch additions coupled with different impeller types and configurations promotes hardwood slurry blending, accommodates the increase in viscosity, and enables quantification of energy and power consumption.