The Piraquê-Açú and Piraquê-Mirim estuarine system (PAPMES) is considered to be a hydrologically unaltered estuary; however, several human activities including introduction of pollutants may have contributed to changes in this system. We have studied hydrocarbons, major elements (Al, Mg, Fe and Mn), trace elements (As, Ba, Cd, Co, Cr, Cu, Li, Ni, Pb, V and Zn), Corg./Ntotal ratio, and δ13C and δ15N stable isotopic composition of organic matter to assess the natural and anthropogenic depositional record in three sediment cores dated by 210Pb geochronology. The sediments showed a strong terrestrial C3 plant contribution to organic matter input in the rivers (−29.2≤δ13C≤−25.1‰; 2.1≤δ15N≤5.3‰; 23.3≤Corg./Ntotal≤53.9), with a higher phytoplankton influence downstream (−29.3≤δ13C≤−20.7‰; 0.4≤δ15N≤6.6‰, and 15.4≤Corg./Ntotal≤34.4). Greater n-alkane concentrations typical of higher plants (nC27, nC29, nC31) confirmed the terrestrial inputs. There was no indication of contamination by petrogenic sources, but relatively high amounts of 17β(H), 21β(H) and 17β(H), 21α(H) terpanes, indicate a possible association with biogenic activities (bacteria). The distributions of major and trace elements were associated with a high lithogenic input and iron and manganese oxides/hydroxides. Although there is little evidence of enrichment by direct human activity, the downstream sediments may be influenced by deforestation for charcoal production which occurred between the 1950s and 70s, exposing soils to weathering and erosion.