As environmental deterioration and global warming arouses more and more attention, identifying cleaner and more environmentally friendly energy sources is of interest to society. In addition to environmental concerns, both the high price of gasoline and the fact that the United States has heavy reliance on imports of energy have driven policymakers to find alternative energy sources. Producing biofuels from energy crops is one such alternative with relatively lower greenhouse gas emissions compared to traditional energy sources. Cellulosic feedstocks such as corn stover, perennial grasses and fast growing trees are regarded as promising energy crops and are expected to help with the energy supply. This study takes a spatially explicit approach to examine fields within a watershed and explores the conditions under which the agricultural land in the watershed can meet the demand of a biorefinery. Costs of two dedicated energy crops, switchgrass and miscanthus, are compared with corn stover. A Matlab program is developed based on a genetic algorithm to minimize production cost subject to biomass production and pollution constraints in the Wildcat Creek Watershed in Indiana, USA. The process of using a genetic algorithm to solve high dimensionality mixed integer optimization problems is discussed. Results indicate that to achieve the required amount of biomass production for a minimum feasible scale thermochemical biorefinery within the watershed, miscanthus must be planted. Miscanthus also helps reduce pollutant levels (total sediment, N and P loadings) when compared to stover removal from continuous corn and corn-soybean rotations. Switchgrass is found to have similar environmental advantages, but is not economically competitive based on preliminary results that require further validation. Corn stover is the lowest cost feedstock considered, however, it results in relatively higher sediment, nitrogen and phosphorus loading than the perennial grasses considered. Relative to the baseline without stover removal, no-till in combination with stover removal results in decreased sediment loading, an increased loading of nitrogen under continuous corn and an increase in phosphorus (except at the 50% removal rate from continuous corn). There is clear tradeoff among cost, production and environmental improvement.