This study investigates the Late Quaternary sediment distribution of the Zambezi turbidite system (Mozambique Channel, Western Indian Ocean) from a set of piston cores that characterizes the sedimentation in the Intermediate Basin and in the proximal and distal parts of the Zambezi Fan. Sedimentological and geochemical analyses permit to define variations in sediment composition, sediment accumulation rates and timing of turbiditic deposits over the past 720 kyr. Our study reveals low sediment inputs and rare turbiditic deposits in the Zambezi turbidite system, and the deep (>2,500 m) Mozambique Channel in general, over the studied time interval. The reconstruction of the terrigenous flux in the upper part of the system suggests monsoon-related precipitation changes as the main forcing for riverine inputs variability in the Zambezi system. However, the occurrence of turbiditic deposits in the cores suggests that there is no genetic link between their triggering and evolving climate and sea-level conditions, thus emphasizing transformation of failed (slide-generated) sediment from the continental slope as the main initiation process for turbidity currents in the Zambezi system. Finally, our data highlight regional-scale changes in sedimentary facies through time, interpreted as successive ‘on-off’ switches in the activity of the distal Zambezi Fan, and by extension, regional-scale depocenter shifts. The last one likely occurred at 350 ± 42 kyr, and is concomitant with a significant increase in terrigenous inputs into the proximal Intermediate Basin. It is speculated that this depocenter shift is related to a major southward migration of the Zambezi delta.