Colombian mango production, which exceeded 261,000 t in 2020, generates about 40% of the whole fruit as solid waste, of which more than 50% are seed kernels (over 52,000 t solid by-product); though none is currently used for commercial purposes. This study reports the results of the supercritical carbon dioxide (scCO₂) extraction of an oil rich in essential fatty acids (EFAs) from revalorized mango seed kernels and the optimization of the process by the Response Surface Methodology (RSM). In pilot-scale scCO₂ experiments, pressure (23–37 MPa) and temperature (52–73 °C) were varied, using 4.5 kg of CO₂. The highest experimental oil extraction yield was 83 g/kg (37 MPa and 63 °C); while RSM predicted that 84 g/kg would be extracted at 35 MPa and 65 °C. Moreover, by fine-tuning pressure and temperature it was possible to obtain an EFA-rich lipid fraction in linoleic (37 g/kg) and α-linolenic (4 g/kg) acids, along with a high oleic acid content (155 g/kg), by using a relatively low extraction pressure (23 MPa), which makes the process a promising approach for the extraction of oil from mango waste on an industrial scale, based on a circular economy model.