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Paleoenvironmental and paleoecological aspects of the Río Loro Formation (Paleogene, northwestern Argentina) were analyzed. In the type locality, four main sedimentary facies were recognized. Facies 1 (coarse-grained to pebbly amalgamated sandstones) record sedimentation in braided channels. Facies 2 (structureless to faintly laminated mudstones) and Facies 3 (interbedded mudstones with sandstones) are ascribed to deposition in distal to proximal floodplain settings, respectively. Facies 4 (coarse to medium-grained sandstone) is interpreted as deposited in meandering channels. Insect trace fossils, ascribed to nesting structures, were recognised particularly in facies 1 and 4. The recognized facies were grouped in a main facies association which allows interpretating a deposition in a complex multi-channel fluvial system with relatively stable muddy floodplain areas. Within this system, seasonal humid to dryer conditions favored biota substrate colonization and soil-forming processes. Well-preserved mammalian and reptilian remains were recognized in sandy mudstone deposits of Facies 3, showing low weathering stages (mainly stages 1 and 2) and the absence of signs of abrasion. These aspects, along with the presence of some articulated remains and their integration with the paleoenvironmental framework, suggest that skeletal pieces suffered an early burial after partial disarticulation, possibly by splays during major floods. The inferred habits of some of the taxa recorded are consistent with proximity to freshwater sources, vegetated areas, and seasonality. This multidisciplinary approach contributes to the understanding of paleoenvironmental and paleontological attributes of the Río Loro Formation and represents a basis for future surveys on this unit and its remarkable fossil record.