The influence of a sophisticated water distribution system on urban development in Roman times is tested against the impact of Vesuvius volcanic activity, in particular the great eruption of AD 79, on all of the ancient cities of the Bay of Naples (Neapolis). Written accounts on urbanization outside of Rome are scarce and the archaeological record sketchy, especially during the tumultuous fifth and sixth centuries AD when Neapolis became the dominant city in the region. Here we show that isotopic ratios of lead measured on a well-dated sedimentary sequence from Neapolis’ harbor covering the first six centuries CE have recorded how the AD 79 eruption was followed by a complete overhaul of Neapolis’ water supply network. The Pb isotopic signatures of the sediments further reveal that the previously steady growth of Neapolis’ water distribution system ceased during the collapse of the fifth century AD, although vital repairs to this critical infrastructure were still carried out in the aftermath of invasions and volcanic eruptions.