Coastal salt marshes and estuaries provide valuable ecosystem services, yet are susceptible to alteration from human activities. Records of past environmental change in these ecosystems can elucidate relationships between human activities, such as land-use practices, and physical and ecological processes, such as sediment accretion and vegetation changes. To reconstruct the environmental history of one such site, we present inferences based on analysis of sediment cores (including magnetic susceptibility, loss-on-ignition, and pollen) from the Morro Bay salt marsh, located in California’s central coast in the USA. Chronologic control for the sediments was established using radiocarbon dates, a spike in lead (Pb) sourced from gasoline combustion exhaust, and the first identified occurrences of the non-native taxa Erodium cf. cicutarium (filaree) and Eucalyptus. We demonstrate that the Morro Bay watershed was significantly altered following Spanish settlement in the region. Environmental changes associated with livestock grazing and agriculture become evident in the data starting after 1772 CE, when the Mission San Luis Obispo de Tolosa was established nearby. The most prominent changes observed are an increase in the accumulation rate of terrigenous sediment, organic matter, and carbonates, as well as a reduction in arboreal taxa concomitant with increased abundances of shrubs, herbs, and grasses. The expansion of Salicornia (pickleweed) in the 19th century suggests the salt marsh expanded at this time due to increased sediment accumulation and a resulting increase in local elevation. The timing and character of changes recorded in the Morro Bay salt marsh sediments are similar to those documented across California in estuaries, marshes, lakes, and meadows, demonstrating the magnitude of the impacts of European settlement and associated land-use practices in this region.