The scale-up of mechanochemical methods could play a transformative role in making manufacturing processes in the pharmaceutical industry greener by eliminating solvent use and recovery. Combined with energy-efficient continuous processing that consolidates reaction steps, mechanochemistry's environmental and economic benefits may translate across product supply chains. Here, we evaluate numerous sustainability and green chemistry metrics for producing nitrofurantoin, an active pharmaceutical ingredient (API), via mechanochemical continuous twin-screw extrusion (TSE) and conventional solvent-batch synthesis methods. We find a significant reduction in all metrics for TSE including energy, climate change, and human and ecological health, as well as cost due to reducing excess reactant consumption and eliminating solvents while maintaining high product selectivity. In addition, replacing the direct energy source to drive the chemical reaction from mostly thermal to electrical sources does not increase the net life cycle energy consumed to produce functionally equivalent API. We conclude that mechanochemical synthesis via TSE holds multiple sustainability benefits for manufacturing APIs and potentially other chemical products.