A coupled study of fluid inclusions and one-dimensional basin modeling allowed the reconstruction of the early hydrocarbon filling history of the main petroleum systems of the Potiguar Basin, Brazil. Confocal laser scanning microscopy, microthermometry and fluorescence spectra measurements were used to model PVTx properties of petroleum inclusions in samples from the onshore Lorena and the offshore Ubarana oilfields. The fluid inclusion data and basin modeling suggest that the initial filling of the Lorena reservoir (Pendência Formation) occurred during the rift stage in two scenarios at 62.7–80.6 °C (11–16.8 MPa): (i) the late rift phase in the Barremian–Early Aptian (ca. 129–124 Ma) or during the beginning of the uplifting phase in the Aptian (ca. 118–117 Ma). In the Ubarana Oilfield, hydrothermal fluids migrated alongside petroleum during the reservoir initial filling. Fluid inclusion homogenization temperatures for both the Açu (mode interval of homogenization temperatures, Th(LV→L)mode interval = 124–128 °C) and Ponta do Mel (Th(LV→L)mode interval = 115–130 °C) formations are higher than the present-day reservoir temperature (110 °C). Isochoric modeling of saddle dolomite-hosted fluid inclusions from the Ponta do Mel Formation indicates trapping temperatures between 128.9 and 133.1 °C and pressures between 10.6 and 12.9 MPa. Temperatures and salinities (16 and 20 mass % equivalent in NaCl + CaCl2) of aqueous inclusions hosted in saddle dolomite are similar to those of the fluid inclusions trapped in hydrothermal minerals in Mississippi Valley-Type Pb–Zn deposits. No specific timing can be suggested for the hydrothermal event in Ubarana Oilfield. However, this atypical (hydrothermal) petroleum system could be linked to two possible scenarios: (i) the onset of petroleum migration of the Alagamar Formation during the Cenozoic Macau (ca. 48–8.8 Ma) magmatic event; or (ii) an earlier activity of the petroleum system, prior to the peak oil generation (50–10 Ma).