The worldwide evidence of human activities on the environment led the scientific community to recognize a new geologic time unit known as the Anthropocene. Since the twentieth century, the estuaries have been largely impacted by urbanization and industrialization needs driven by population and economic growth. To assess the contamination, provenance, and fluxes of trace elements (As, Cr, Cu, Ni, Pb, Sc, V and Zn) over the last century, a geochemical and chemometric technique was employed in sediment cores of the Santos and São Vicente Estuarine System (SSVES), an industrial and port region of international importance. The results indicated low contamination, with the highest enrichment factors (EF) for Cu (EF = 3.1), Pb (EF = 2.7), Zn (EF = 2.4) and As (EF = 2.3) found next to the harbor area. The Pre-industrial records confirm the relatively high concentrations of As and its naturally enriched occurrence on the Brazilian shelf. Sediment accumulation rates and trace element fluxes showed a general increase over the years, since the early 1960s, associated with the “Great Acceleration” of the mid-twentieth century. These alterations are human-induced and include urbanization and industrialization. Nonetheless, as the contents and enrichment of trace elements indicate that the region is not severely polluted, we hypothesize that the contamination in the SSVES is likely related to the drainage and erosion of the urbanized adjacent area, rather than direct disposal of inorganic contaminants from the industrial activity.