Simple Summary The rearing of ruminant animals is an environmental issue related to greenhouse gas emissions, mainly methane. In the current study, a regression analysis was carried out to obtain a regression equation able to successfully estimate methane production of lambs fattened under intensive feeding systems from their meat fatty acid profile and average body weight during the fattening period. The optimized model exhibited high precision, accuracy and reproducibility. It showed a clear relationship between methane emissions and the fatty acid profile of lamb meat. Our predictive model indicates that fatty acid contents in intramuscular fat could be used to establish the environmental footprint of meat from ruminants. Methane (CH4) emissions pose a serious problem for the environmental sustainability of ruminant production. The aim of the present study was to explore the usefulness of the intramuscular fatty acid (FA) profile to estimate CH4 production of lambs fattened under intensive feeding systems. A statistical regression analysis of intramuscular FA derived from ruminal metabolism was carried out to assess the best predictive model of CH4 production (g/d) in lambs fed with different diets. CH4 was calculated with three distinct equations based on organic matter digestibility (OMD) at maintenance feeding levels. The OMD of the experimental diets was determined in an in vivo digestibility trial by means of the indicator method. Regression models were obtained by stepwise regression analysis. The three optimized models showed high adjusted coefficients of determination (R-adj(2) = 0.74-0.93) and concordance correlation coefficients (CCC = 0.89-0.98), as well as small root mean square prediction errors (RMSPE = 0.29-0.40 g/d). The best single predictor was vaccenic acid (trans-11 C18:1), a bioactive FA that is formed in the rumen to a different extent depending on dietary composition. Based on our data and further published lamb research, we propose a novel regression model for CH4 production with excellent outcomes: CH4 (g/d) = -1.98 (+/- 1.284)-0.87 (+/- 0.231) x trans-11 C18:1 + 0.79 (+/- 0.045) x BW (R-adj(2) = 0.97; RMSPE = 0.76 g/d; CCC = 0.98). In conclusion, these results indicate that specific intramuscular FA and average BW during fattening could be useful to predict CH4 production of lambs fed high concentrate diets.