Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity. In the present work, the use of high-throughput technologies allowed us to determine the plasma lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5 to 120 years. The non-targeted approach revealed a specie-specific lipidomic profile that accurately predicts the animal longevity. The regression analysis between lipid species and longevity demonstrated that the longer the longevity of a species, the lower is its plasma long-chain free fatty acid (LC-FFA) concentrations, peroxidizability index, and lipid peroxidation-derived products content. The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence. These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.