The Xolapa Complex of southern Mexico is composed of mid-crustal arc-related gneisses of poorly resolved ages, intruded by undeformed Cenozoic calc-alkaline plutons. Twelve undeformed and deformed tonalitic/granodioritic samples from three transects across the Sierra Madre del Sur (Acapulco, Puerto Escondido, and Puerto Angel) were chosen for U-Pb zircon analysis. The measurements were performed on single crystals of zircons, using a multiple-collector laser-ablation inductively coupled plasma–mass spectrometer (MC-LA-ICP-MS). About 20–30 crystals were measured from each sample. Three gneisses and migmatites from the eastern transect (Puerto Angel), located 30–42 km from the coast, yielded Grenville-aged zircons (970–1280 Ma), suggesting that the samples represent Oaxacan basement, not deformed Xolapa Complex. The central transect (Puerto Escondido) yielded Oligocene ages (25–32 Ma) on undeformed plutons as well as mid-Mesozoic and Permian ages on gneisses. Most samples along the Puerto Escondido transect contain inherited ca. 1.1 Ga xenocrystals of zircons. The western transect (Acapulco) yielded Late Jurassic–Early Cretaceous ages (160–136 Ma) on gneisses, and Paleocene (55 Ma) and Oligocene (34 Ma) ages on undeformed plutons, with no inherited Grenville ages. The older ages and xenocrystic zircons in arc-related Xolapa Complex mirror the crustal ages found in neighboring terranes (Mixteca and Oaxaca) to the north of the Xolapa Complex, suggesting an autochthonous origin of Xolapa with respect to its neighboring north-bounding terranes. The new data and previously published ages for Xolapa suggest that metamorphism and migmatization of the deformed arc rocks took place prior to the Cenozoic. Eocene and Oligocene plutons representing renewed arc-related magmatism in the area are common throughout Xolapa, and probably represent the more deeply exposed continuation of the Sierra Madre Occidental arc to the northwest. The available U-Pb data argue against the previously proposed eastward migration of magmatism between Acapulco and Puerto Angel during the Oligocene.