Seismic reflection profiles combined with sediment cores reveal centennial changes in the proximal and distal sedimentation regime in the Rhone River delta system (Lake Geneva), which is dominated by sublacustrine channels. From detailed analyses of the thickness distribution of depositional units and the occurrence of turbidites, at least two shifts of the primarily active sublacustrine channels are inferred for the past 1500 years. The first northward shift is dated at 1480 ± 20 cal AD and was likely linked to a centennial flood in the Swiss Rhone Valley that occurred in 1469 AD and acted either as a direct cause or as a preconditioning factor favoring the shifting. A shift back southward in 1720 ± 90 cal AD may have been caused either by long-term human impact related to the first embankment constructions on the Rhone River or by a natural event such as the 1755 AD Brig earthquake or the centennial flood of 1640 AD. Another important change in the sedimentation regime occurs in 1775 ± 125 cal AD when the onset of Rhone turbidite deposition is recorded in the distal sediments. This relative “progradation” of the Rhone turbidites is certainly due to the disconnection of the Vieux Rhone branch before 1826 and the subsequent first Rhone River correction, starting in 1863 that led to the present single active Rhone subaquatic channel.