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Amongst the rivers draining the mountainous islands of the Indonesian Archipelago, the Sepik River of Papua New Guinea is the largest contributor of solute and particulate material to the world ocean. Sites U1484 and U1485, drilled during International Ocean Discovery Program (IODP) Expedition 363 provide a continuous, similar to 555 kyr long, high-resolution record of mainly siliciclastic slope sedimentation on the northern continental margin of PNG, just offshore the mouth of the Sepik River. Sedimentological analysis, based on a combination of smear slide petrography, particle size analysis, high-resolution physical properties track data and visual core description, offers an unprecedented opportunity to investigate the evolution of this major tropical river throughout changing climate and sea-level conditions during the mid- to late Pleistocene. The Sites U1484 and U1485 sediment records exhibit a dramatic lithologic change at similar to 370 ka: the oldest deposits are dominated by pelagic mud, suggesting that the coarser-grained terrigenous discharge from rivers draining the New Guinea Highlands (including a "proto" Sepik River) was captured before reaching the ocean, when the Sepik River basin was an epicontinental sea. The occurrence of coarser-grained, mass-gravity (mainly hybrid) flows after similar to 370 ka suggests that the epicontinental sea became a more restricted, shallow-water to nonmarine basin, probably due to both basin infilling and the uplift of local coastal ranges. During the last three glacial-interglacial cycles (similar to 300 kyr), this shallow inland basin was strongly affected by global variations in sea level: during sea level lowstands, the Sepik River cut into older sediments and discharged further offshore onto the shallow continental margins, promoting mass-gravity flows. Pelagic mud deposition on the continental margin during the most extreme highstands following deglaciations suggests a return to shallow marine conditions in the Sepik Basin and repositioning of the river mouth further inland, away from the shelf and from the location of the IODP sites. This also indicates that variations in terrigenous fluxes during these extreme highstands were not solely controlled by the intensity of the hydrological cycle and that global sea level variations also influenced sediment deposition. The sequence is interrupted by several massive grain flow deposits, occurring diachronously at Sites U1484 and U1485 and related to a period of intensified tectonic activity between similar to 280 ka and similar to 140 ka. The sedimentologic characteristics of these mass-gravity deposits and their lack of correlation between sites are interpreted as resulting from channelized flows along margin-parallel, fault-controlled channels caused by local and regional failures of the continental margins including the area of the Yalingi Canyon, similar to 50 km north of the sites, where large tsunamigenic events have also occurred in recent years. Time series analyses of magnetic susceptibility and natural gamma radiation (proxies for %sand and %clay content, respectively) indicate that river discharge fluxes were modulated at orbital frequencies (including obliquity-scale cycles), which suggests that precipitation and river discharge were not only linked to precessionally driven shifts in the mean position of the Intertropical Convergence Zone, but also to high-latitude climate change.