The Great Lisbon earthquake has the largest documented felt area of any shallow earthquake and an estimated magnitude of 8.5–9.0. The associated tsunami ravaged the coast of SW Portugal and the Gulf of Cadiz, with run-up heights reported to have reached 5–15 m. While several source regions offshore SW Portugal have been proposed (e.g.— Gorringe Bank, Marquis de Pombal fault), no single source appears to be able to account for the great seismic moment as well as all the historical tsunami amplitude and travel time observations. A shallow east dipping fault plane beneath the Gulf of Cadiz associated with active subduction beneath Gibraltar, represents a candidate source for the Lisbon earthquake of 1755. Here we consider the fault parameters implied by this hypothesis, with respect to total slip, seismic moment, and recurrence interval to test the viability of this source. The geometry of the seismogenic zone is obtained from deep crustal studies and can be represented by an east dipping fault plane with mean dimensions of 180 km (N–S) × 210 km (E–W). For 10 m of co-seismic slip an Mw 8.64 event results and for 20 m of slip an Mw 8.8 earthquake is generated. Thus, for convergence rates of about 1 cm/yr, an event of this magnitude could occur every 1000–2000 years. Available kinematic and sedimentological data are in general agreement with such a recurrence interval. Tsunami wave form modeling indicates a subduction source in the Gulf of Cadiz can partly satisfy the historical observations with respect to wave amplitudes and arrival times, though discrepancies remain for some stations. A macroseismic analysis is performed using site effect functions calculated from isoseismals observed during instrumentally recorded strong earthquakes in the region (M7.9 1969 and M6.8 1964). The resulting synthetic isoseismals for the 1755 event suggest a subduction source, possibly in combination with an additional source at the NW corner of the Gulf of Cadiz can satisfactorily explain the historically observed seismic intensities. Further studies are needed to sample the turbidites in the adjacent abyssal plains to better document the source region and more precisely calibrate the chronology of great earthquakes in this region.