In this work, supercritical fluid extraction (SFE) for the recovery of phenolic antioxidants from papaya agroindustrial waste (seeds) was explored, making use of neat supercritical CO2 and CO2 added with ethanol (CO2-EtOH). A full factorial design played on in order to evaluate the effect of CO2 extraction parameters (temperature between 40 and 60 °C, and pressure between 10 and 30 MPa) on yield and total phenols content (TPC), then ethanol was applied as a co-solvent and its effect on the recovery of phenolics was analyzed. The SFE was compared to the conventional extraction using ethanol. The antioxidant activity of all extracts was evaluated, and the phenolic composition in selected extracts was assessed by HPLC-ESI-MS. The highest extraction yields (21.02–26.46%) and TPC (15.34–34.23 mgGAE/g) were found in extracts obtained with CO2-EtOH and ethanol. Good and selective phenolic recovery was obtained by using CO2-EtOH, (44.81% of TPC recovered). The CO2-EtOH extracts showed high radical scavenging activity and higher antioxidant effect against lipid oxidation. Some phenolic acids and flavonoids were observed in the extracts with better antioxidants properties. The results showed that SFE is a suitable green technology for the phenolic recovery from papaya agroindustrial waste, and also an alternative for its valorization.