Sequential two-dimensional forward modelling of source rock maturation along a north–south 600 km megaregional profile across the northern Gulf of Mexico Basin illustrates the coupled influence of allochthonous salt evolution and overpressure development on source rock maturation. Model results indicate that allochthonous salt evolution strongly affected local and regional source rock maturation, while overpressure development had a minor impact. Within the lower slope portion of the profile (south of the Sigsbee escarpment to the Tabular Salt/Minibasin province), localized thermal lows associated with salt stock development locally retarded the maturation of source rocks, while the slow development of overpressures effected little influence on the maturation. Within the centre of the profile (offshore Louisiana shelf), however, the evolution of allochthonous salt sheets and shallow salt structures locally and regionally lowered the oil generation window. The timing of overpressures in this region, related to the progradation of the Cenozoic marine depocentre, may have accelerated the maturation of middle Eocene source rocks, although the deeper Turonian source rocks had reached maturation at the time of greatest overpressure development. In the northern portion of the profile (southern Louisiana), the Terrebonne salt sheet lowered the oil generation window and retarded the maturation of the middle Eocene source rocks.