The Tiber valley is a prominent feature in the landscape of ancient Rome and an important element for understanding its urban development. However, little is known about the city's original setting. Our research provides new data on the Holocene sedimentary history and human-environment interactions in the Forum Boarium, the location of the earliest harbor of the city. Since the Last Glacial Maximum, when the fluvial valley was incised to a depth of tens of meters below the present sea level, 14C and ceramic ages coupled with paleomagnetic analysis show the occurrence of three distinct aggradational phases until the establishment of a relatively stable alluvial plain at 6-8 m a.s.l. during the late 3rd century BCE. Moreover, we report evidence of a sudden and anomalous increase in sedimentation rate around 2600 yr BP, leading to the deposition of a 4-6m thick package of alluvial deposits in approximately one century. We discuss this datum in the light of possible tectonic activity along a morpho-structural lineament, revealed by the digital elevation model of this area, crossing the Forum Boarium and aligned with the Tiber Island. We formulate the hypothesis that fault displacement along this structural lineament may be responsible for the sudden collapse of the investigated area, which provided new space for the observed unusually large accumulation of sediments. We also posit that, as a consequence of the diversion of the Tiber course and the loss in capacity of transport by the river, this faulting activity triggered the origin of the Tiber Island.