The effect of the use of rootstock Criollo on the susceptibility of Manila mango fruit to infestation by Anastrepha obliqua (Macquart) was determined in the present investigation. Growth, quality parameters (Soluble solids content (%), citric acid content (%), firmness, monoterpene volatiles (3-carene, limonene, α-pinene, and β-myrcene), main flavonoids content (milligrams/100 g fresh pulp), and larvicidal activity of methanolic extracts, as well as the degree of infestation during preharvest development of the fruits were analyzed. The results indicated that the rootstock did not have any significant effect on growth, soluble solids content, or citric acid content; although it increased firmness as well as 3-carene levels and main flavonoids content, resulting in a greater resistance to infestation by A. obliqua. The obtained results support the use of this rootstock because of the beneficial effects observed on the resistance of mango fruit to infestation by this fruit fly.