During the last decades, rivers and their deposits in different regions were intensively studied to better understand the late-Quaternary landscape evolution and former human activities. One proxy for paleoecological and paleoclimatic reconstructions is the analysis of gastropods (snails) from carbonatic river sediments. In the scope of this study, we investigated gastropod assemblages from a Holocene fluvial sediment–paleosol sequence at the upper Alazani River in the southeastern Caucasus. On the one hand, we aimed to derive reliable independent information about possible long-lasting human activity since the late Neolithic–Chalcolithic in the upper Alazani floodplain. This was formerly suggested by n-alkane biomarker vegetation reconstructions from the fluvial sediments. However, the reliability of that method is still debated. On the other hand, we aimed to obtain reliable information about a formerly suggested, possibly tectonic-driven, large-scale shift of the river course during the Late Holocene. In agreement with the n-alkane biomarkers, our results demonstrate that the studied site was free of the natural forests during the Early and Middle Holocene until ca. 4.5 cal kyr BP. Since this contrasts with a pollen-based vegetation reconstruction from a neighboring floodplain that was covered with forests during that time, the open vegetation in the upper Alazani valley was probably caused by continuous settlement activity as is also indicated by archeological finds in the sequence. Therefore, using our paleoecological proxies it is possible that we identified a settlement center in the upper Alazani floodplain that was populated from the late Neolithic–Chalcolithic. This center was not known thus far, since the settlement remains are covered by thick floodloam today that hindered their detection during archeological surface surveys. Therefore, our findings suggest that the area in the southern Caucasus region that was settled during the late-Neolithic–Chalcolithic period should have been larger than was known thus far. Furthermore, increasing contributions of wetland gastropods since ca. 4 cal kyr BP confirm a local shift of the river course towards the investigated site during the Late Holocene, possibly linked with ongoing tectonic activity. However, in contrast to former suggestions our gastropod assemblages indicate a slow rather than abrupt process. Our study demonstrates the high value of gastropod assemblages for geoarcheological and geomorphological research in floodplains with carbonatic river sediments at both a regional and local spatial scale.