Papaya (Carica papaya L.) is one of the most commonly planted and consumed fruits in the world, especially in tropical and subtropical areas. In recent years, due to the diverse range of nutritional value and medicinal properties of bioactive substances possessed in papaya, papaya fruit and their by-products have gained more attention. The present study aimed to characterize the different parts (pulp, peel, and seed) of two varieties of papaya (yellow- and red-fleshed) at different stages of ripeness (unripe and ripe) for their phenolic compounds using liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS). The phenolic content and antioxidant activity were detected through several assays. Yellow-fleshed unripe papaya seed showed the highest total phenolic content (TPC) (4.73 mg GAE/g). Red-fleshed ripe papaya peel exhibited the highest level of total tannin content (TTC) with 1.98 mg CE/g, while red-fleshed unripe peel exhibited the highest total flavonoid content (TFC) with 2.78 ± 0.04 mg QE/g. In terms of antioxidant potential, yellow-fleshed unripe papaya peels had the highest radical scavenging activities for the DPPH, ABTS, and TAC tests. LC-ESI-QTOF-MS/MS experiment successfully tentatively identified 118 phenolic compounds in total, including phenolic acids (35), flavonoids (61), stilbenes (3), lignans (7) and other polyphenols (12) in all papaya samples. Analyses indicate that the three different parts of the papaya fruit are potential sources of phenolic compounds, particularly the peel. The results of this study provide practical data for the potential application of papaya fruit as a functional food ingredient in the food, pharmaceutical and medicinal industries.