Land clearing, river impoundments, and other human modifications to the upland landscape and within estuarine systems can drive coastal change at local to regional scales. However, as compared with mid-latitude coasts, the impacts of human modifications along sediment-starved formerly glaciated coastal landscapes are relatively understudied. To address this gap, we present a late-Holocene record of changing sediment accumulation rates and sediment sources from sediment cores collected across a tidal flat in the Merrimack River estuary (Mass., USA). We pair sedimentology, geochronology, bulk- and stable-isotope organic geochemistry, and hydrodynamic simulations with historical data to evaluate human and natural impacts on coastal sediment fluxes. During the 17th to 19th centuries, accumulation rates increased by an order of magnitude in the central tidal flat, likely in response to enhanced delivery of terrestrial sediment resulting from upland deforestation. However, the overall increase in accumulation (0.56–2.6 mm/year) within the estuary is subtle and spatially variable across the tidal flats because of coincident anthropogenic land clearing and dam building, upland sediment storage, and estuarine hydrodynamics. This study provides insight into the response of formerly glaciated fluvial-coastal systems to human modifications, and underscores the role of estuarine environmental conditions in modifying upland signals of land-use change.