Abstract Synthetic nitrogen (N) fertilization has helped boost agricultural yields, but it is also responsible for direct and indirect greenhouse gas (GHG) emissions. Fertilizer-related emissions are also promoted by irrigation and manure application, which has increased with livestock industrialization. Spanish agriculture provides a paradigmatic example of high industrialization under two different climates (temperate and Mediterranean) and two contrasting water management regimes (rainfed and irrigated). In this study, we estimated the historical evolution of the C footprint of N fertilization (including all the life cycle GHG emissions related to N fertilization) in Spanish agriculture from 1860 to 2018 at the province level (50 provinces) for 122 crops, using climate-specific N₂O emission factors (EFs) adjusted to the type of water management and the N source (synthetic fertilizer, animal manure, crop residues and soil N mineralization) and considering changes in the industrial efficiency of N fertilizer production. Overall, N-related GHG emissions increased ∼12-fold, up to 10–14 Tg CO₂e yr⁻¹ in the 2010s, with much higher growth in Mediterranean than in temperate areas. Direct N₂O EFs of N fertilizers doubled due to the expansion of irrigation, synthetic fertilizers and liquid manure, associated with livestock industrialization. Synthetic N production dominated the emissions balance (55%–60% of GHGe in the 21st century). Large energy efficiency gains of industrial fertilizer production were largely offset by the changes in the fertilizer mix. Downstream N₂O emissions associated with NH₃ volatilization and NO₃ ⁻ leaching increased tenfold. The yield-scaled carbon footprint of N use in Spanish agriculture increased fourfold, from 4 and 5 Mg CO₂e Mg N⁻¹ to 16–18 Mg CO₂e Mg N⁻¹. Therefore, the results reported herein indicate that increased productivity could not offset the growth in manufacture and soil emissions related to N use, suggesting that mitigation efforts should not only aim to increase N use efficiency but also consider water management, fertilizer type and fertilizer manufacture as key drivers of emissions.