The impacts of coastal changes and human land use on depositional processes, ecological conditions, geomorphic evolution and harbor works at the archaeological site of Lattara, one of the oldest cities of the northwestern Mediterranean built in a deltaic environment, were investigated from a multi-proxy approach based on sedimentological, biological and geochronological analyses. A distributary channel connected to the ancient harbor of Lattara was deepened and channelized around 200 cal BCE. The drastic increase in water depth caused by channelization was associated with increased flow competence and bedload transport, and could have improved navigation in the harbor area. By contrast, high accumulations of anthropogenic deposits in the channelized stream from the second century CE seem to have negatively affected sediment transport conditions by reducing bedload flux. The construction of a cobble pavement on the western bank of this channelized stream in the fourth century CE was contemporaneous with a sharp decrease in bedload transport showing an abrupt transition to a low energy environment such as in abandoned channels. A drainage ditch was then dug in the deposits of the channelized stream during the Medieval Warm Period, in a context of land use intensification and increased river flooding that led to the deposition of coarser sediments.