The Paleogene infill of the eastern Golfo San Jorge Basin, Patagonia, Argentina, is composed of marine (Salamanca Formation) and terrestrial (Grupo Rio Chico and lower Sarmiento Formation) deposits. The Rio Chico Group is a fluvial, pedogenically modified succession interlayered with eolian volcaniclastic deposits during the Eocene. Several authors have highlighted the stratigraphic significance and usefulness of strongly developed paleosols in the definition of sequence stratigraphic studies. Even though the area hosts abundant geological and paleopedological data, no large-scale (i.e., basin-scale) stratigraphic architectural correlation including paleosols and relationships within the sequence stratigraphic context had hitherto been carried out. By integrating previously published and unpublished data sets, this paper proposes a sequence stratigraphic framework for the middle Danian–middle Eocene successions of the eastern Golfo San Jorge Basin. Here, spatio-temporal changes in fluvial/alluvial architecture of the Paleogene infill allow us to define four depositional sequences (S), limited by sequence boundaries (SB) that internally presents a low-accommodation system tract (LAST), and a high-accommodation system tract (HAST). Part of these sequences occur as fining-upwards fluvial successions that are pedogenically modified on top by strongly developed paleosols, or are erosively overlain by the coarse-grained base of the following sequence without the development of well-developed paleosols. The sedimentological and paleopedological analysis of the four sequences identified for the early Paleogene infill of the basin indicates that the interplay between subsidence, base level, and climate controlled both fluvial style and landscape evolution, as well as soil development. Volcaniclastic supply also played a significant role, especially during the Eocene.Centro de Investigaciones Geológicas