<p>Weak layers have been identified as lithological contrasts on continental slopes to precondition giant submarine landslides. Although sea-level variations are well known to generate weak layers on glaciated continental margins at high latitudes, their role on non-glaciated continental slopes, mostly at low latitudes, remains poorly constrained. Here, we combine seismic and well-log data, showing that the glide plane beneath the giant Baiyun Slide Complex in the South China Sea is located at a lithological interface, within a relatively coarse-grained unit that was deposited during the late Pliocene sea-level drop. Fluid migration pathways are further identified in the underlying fine-grained unit, which was deposited during the early Pliocene sea-level rise. Sea-level variations are therefore proposed to form unstable sedimentary sequences by the deposition of interbedded fine- and coarse-grained sediments. Considering the global records of sea-level variations and consequent lithological contrasts on non-glaciated slopes, our results shed light on the development of slope instability in low-latitude oceans.</p>