The Coastal Batholith of central Chile between 31 and 34°S represents a locus of long-lived (c. 200 Ma) plutonic activity. It is composed of four plutonic complexes: Santo Domingo, Limarı́, Papudo–Quintero and Illapel. These complexes, which occur as north-trending discontinuous belts that decrease in age eastward, were emplaced during four major episodes of arc magmatism. The Santo Domingo Complex (Carboniferous) comprises hornblende–biotite bearing tonalites and granodiorites with abundant mafic enclaves, and enclave-free granites. The association of enclave-bearing granitoids and enclave-free granites resulted from different degrees of mixing of crustal- and mantle-derived magmas. The Limarı́ Complex (Lower Jurassic) is a bimodal association of crustal leucogranites and mantle-derived gabbros. The lithology of the Papudo–Quintero Complex (Middle Jurassic) varies from hornblende–pyroxene diorite to biotite granite. The main rock types, namely tonalites and granodiorites, commonly contain mafic enclaves. The granitoids and the enclaves have remarkably similar REE patterns and are similar in Sr–Nd isotope composition, which suggest that they represent a cogenetic suite of mantle origin. The Illapel Complex (Cretaceous) consists of hornblende bearing tonalites, trondhjemites and granodiorites that resemble the rocks of TTG suites. The ε Nd values and initial 87 Sr/ 86 Sr ratios (Sr i) for the mafic rocks of the Carboniferous Complex ( ε Nd: −2.0 and −3.5; Sr i: c. 0.7057) differ markedly from those of the Mesozoic mafic rocks ( ε Nd: +1.9 to +5.4; Sr i: 0.7033 to 0.7039), the Cretaceous rocks being the most depleted with regard to Sr–Nd. A change from Carboniferous lithosphere-dominated sources to Mesozoic asthenosphere-dominated sources of the magmas that started in the Early Jurassic is recognized. Slab components can be recognized in the source of the Cretaceous rocks. The crustal source of the Lower Jurassic leucogranites was more isotopically depleted and refractory than that of the Carboniferous granites. On the other hand, no crustal participation in the origin of the Middle Jurassic and Cretaceous felsic granitoids is recognized; they are differentiated from mantle-derived magmas. Progressive removal of old lithospheric mantle during the Mesozoic due to a process of lithospheric delamination would explain the profound change in the subcrustal source, as well as the melting and modification towards a more refractory nature of the continental crust.