© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Agricultural and forestry residues, animal manure and municipal solid waste are replenishable and widely available. However, harnessing these heterogeneous and diffuse resources for energy requires a holistic assessment of alternative conversion pathways, taking into account spatial factors. Here, we analyse, from a life-cycle assessment perspective, the potential renewable energy production, net energy gain and greenhouse gas (GHG) emission reduction for each distinct type of waste feedstock under different conversion technology pathways. The utilization of all available wastes and residues in the contiguous United States can generate 3.1–3.8 exajoules (EJ) of renewable energy, but only deliver 2.4–3.2 EJ of net energy gain, and displace 103–178 million tonnes of CO2-equivalent GHG emissions. For any given waste feedstock, looking across all US counties where it is available, except in rare instances, no single conversion pathway simultaneously maximizes renewable energy production, net energy gain and GHG mitigation.