The evolution of the Triassic–Cretaceous Cuyo Basin, located in the Andean Precordillera (NW Argentina), was mainly controlled by extensional–transtensional tectonics along NW-trending structures inherited from Paleozoic sutures. Stratigraphic and isotopic studies are herein presented in order to constrain the sedimentary infilling and source areas, as well as the age of Triassic strata related to the active faulted margin of the Cacheuta sub-basin. The whole stratigraphic package of the Cuyo Basin is interpreted as a second-order depositional sequence, comprising lowstand (alluvial fan deposits), transgressive (fluvial-deltaic and lacustrine deposits), and high-stand (oxidized lacustrine and high-sinuosity fluvial deposits) systems tracts. This stacking pattern was mainly controlled by the interplay between sedimentary influx and accommodation space, with important volcaniclastic contribution, especially during the early stages of basin development. Sm-Nd depleted-mantle model ages (TDM) for both basement and volcano-sedimentary samples range from 867 to 1345 Ma. All samples have negative ϵNd (t) values (−0.33 to −5.02). Basal deposits present older TDM model ages compared to intermediate-positioned deposits, and upper deposits present a wider range of model ages. This time-integrated factor correlates with paleo-current data, which indicate changes in the source areas through time. The Nd isotopic signature also suggests that sources of sediments for the Cacheuta sub-basin during the Triassic were restricted to units of Mesoproterozoic (Grenvillian) age, probably related to the Cuyania terrane. The U-Pb sensitive high-resolution ion microprobe (SHRIMP) zircon age of 243 ± 5 Ma, obtained in juvenile magmatic zircons from a lithoclast-free ignimbrite interlayered within the basal alluvial fan facies of the Cacheuta sub-basin, places the lowstand deposits in the Olenekian and establishes a potential chronostratigraphic horizon for future correlations.