The San Francisco Estuary, in central California, has several long-running monitoring programs that have been used to reveal human-induced changes throughout the estuary in the last century. Here, we pair synoptic records of particulate organic matter (POM) composition from 1990–1996 and 2007–2016 with more robust long-term monitoring program records of total suspended sediment (TSS) concentrations generally starting in the mid-1970s to better understand how POM and TSS sources and transport have shifted. Specifically, POM C:N ratios and stable isotope values were used as indicators of POM source and to separate the bulk POC pool into detrital and phytoplankton components. We found that TSS and bulk POC sources have shifted significantly across the estuary in time and space from declines in terrestrial inputs. Landward freshwater and brackish water sites, in the Delta and near Suisun Bay, witnessed long-term declines in TSS (32 to 52%), while seaward sites, near San Pablo Bay, recorded recent increases in TSS (16 to 121%) that began to trend downwards at the end of the record considered. Bulk POM C:N ratios shifted coeval with the TSS concentration changes at nearly all sites, with mean declines of 12 to 27% between 1990–1996 and 2007–2016. The widespread declines in bulk POM C:N ratios and inferred changes in POC concentrations from TSS trends, along with the substantial declines in upstream TSS supply through time (56%), suggest measurable reductions in terrestrial inputs to the system. Changes in terrestrial TSS and POM inputs have implications for biotic (e.g., food web dynamics) and abiotic organic matter cycling (e.g., burial, export) along the estuarine continuum. This work demonstrates how human-generated environmental changes can propagate spatially and temporally through a large river-estuary system. More broadly, we show how underutilized monitoring program datasets can be paired with existing (and often imperfect) synoptic records to generate new system insight in lieu of new data collection.