Abstract The meat industry in the US generates considerable amount of slaughterhouse waste (SHW), which is typically converted into more useable products through the rendering process. Although rendering generates sellable fat and meal commodities, it has large environmental impacts because it is energy intensive. Anaerobic digestion (AD) is a promising technology for treating SHW and reducing environmental impact through biogas production to generate heat or electricity, as well as by enabling nutrient recovery and pathogen reduction. This study compared the life-cycle energy use and global warming impact of treating SHW with traditional rendering with AD to produce heat and electricity. The study also considered the co-digestion of SHW with the organic fraction of municipal solid waste (OFMSW) and sewage sludge. A cradle-to-grave life-cycle assessment (LCA) method was used to quantify the energy use and greenhouse gas (GHG) emissions of these systems for treating SHW. We compared three scenarios: (1) AD of SHW, (2) Co-AD of SHW with OFMSW, and (3) Co-AD of SHW with sewage sludge to reference systems of simple rendering and composting. The study findings revealed that the total cradle-to-gate energy use and GHG emissions by treating SHW with AD and co-AD were 0.5−6.7 GJ/1000 kg-SHW and 400−834 kg-CO₂-eq/1000 kg-SHW, whereas for the rendering control scenarios total cradle-to-gate energy use and GHG emissions were 1.9 GJ/1000 kg-SHW and 96.4 kg-CO₂-eq/1000 kg-SHW, respectively. However, considering all the benefits of treating SHW with co-AD, including the displacement of fossil fuel and electricity and nitrogen fertilizers generated as system outputs, these systems perform better than the rendering process. Compared to the reference systems, the GHG reduction potential of treating SHW with co-AD varied between 426.8 and 524.0 kg-CO₂-eq/1000 kg-SHW. Among all input parameters, methane (CH₄) leak from the AD system, and nitrogen fertilizer displacement were the most sensitive parameters affecting the results. By implementing AD of SHW in meat industries in the southeast US, the energy production and GHG emissions reduction potential were estimated to be 22–29 × 10⁶ GJ and 1.6–2.0 × 109 kg-CO₂-eq per year, respectively. The results indicate that the AD of SHW can substantially reduce GHG emissions of the US meat industry as well as produce bioenergy to provide energy security in the US.