Feeding the world’s population sustainably is a major challenge of our society, and was stated as one of the key priorities for development cooperation by the European Union (EU) policy framework on food security. However, with the current trend of natural resource exploitation, food systems consume around 30% of final energy use, generating up to 30% of greenhouse gas (GHG) emissions. Given the expected increase of global population (nine billion people by 2050) and the amount of food losses and waste generated (one-third of global food production), improving the efficiency of food systems along the supply chain is essential to ensure food security. This study combines life-cycle assessment (LCA) and data envelopment analysis (DEA) to assess the efficiency of Spanish agri-food system and to propose improvement actions in order to reduce energy usage and GHG emissions. An average energy saving of approximately 70% is estimated for the Spanish agri-food system in order to be efficient. This study highlights the importance of the DEA method as a tool for energy optimization, identifying efficient and inefficient food systems. This approach could be adopted by administrations, policy-makers, and producers as a helpful instrument to support decision-making and improve the sustainability of agri-food systems.