The sequence stratigraphy of the Lutetian–Langhian series in the Gulf of Gabes basin was defined using cuttings from 50 wells, wireline logs, biostratigraphic data and seismic data. The seismic profiles display a shallow inner shelf passing northeastward to an outer shelf break. Our study helps constrain the depositional and tectonic constraints for hydrocarbon targets. Indeed, syndepositional tectonics and related subsidence and eustatism as well, were found to exert remarkable control on the source-rock and oil-reservoir formations and spatiotemporal repartitions. Detrital facies in the inner shelf pass seaward into a broad carbonate shelf and then into storm-influenced turbidites; whereas marls in the deep shelf and outer basin extend onto the inner-shelf during major highstands. Three major supersequences were identified and each of these comprised multiple third order sequences. The lower supersequence (Lutetian–Priabonian) contains marls interceded with inner-shelf skeletal carbonates which reflect shelf flooding due to rise in sea level. The second supersequence (Rupelian–Burdigalian) bears clays and sands admixed with foraminifered carbonates at the base. Rapid flooding and progradation of shelf carbonate sediments (Vascus Horizon and Ketatna Fm) reflect eustatic lowering. These deposits grew basinward into pelagic marls enriched in organic matter and interceded with limestones (Salammbô Fm). A variety of seismic patterns of the Ypresian–Langhian sequences, notably the concave/lens-shaped ones are associated with transparent seismic facies and are thought to be accounted for by tectonically subsiding depositional settings. Faulting and associated subsidence have caused uplapping seismic reflection patterns of sequences dating the Lutetian to Middle Langhian times. The tectonic pulses and flower faults striking to the NW, with antithetic branches continuously reactivating in the study time interval, caused subsidence and basin margin steepening toward the northeast. In contrast, the west and southwest parts of the basin, tectonically expulsed in the form of a broad paleohigh, were the sites for platform carbonates interfingering with episodes of pelagic sedimentation. A major gap of the Upper Eocene is due to a compressive tectonic period. The Ketatna Fm shows concordant and rather transparent seismic facies, thus contrasting with coeval pelagic intervals with dipping of internal seismic reflections due to intervening normal faulting. A broad transgression during the Middle Langhian deposited the third supersequence due to global warming and subsequent rise in sea level. The carbonate sequences in the Reineche Member, the Ketatna and the Aïn Ghrab formations are notably thick and are proven gas and oil reservoirs.