In January 1531, the Tagus River Estuary was hit by a strong earthquake, the intensity of which in Lisbon was, according to relevant authors, greater than that of the 1755 earthquake. It was cited by most of the European annalists of the time and was responsible for the destruction of structures, the loss of lives, and enormous panic, thus making it one of the most disastrous earthquakes in the history of Portugal. If we give credit to the detailed descriptions, the maximum intensity was probably X MSK. According to our study, the seismic event was probably caused by the Lower Tagus fault zone (LTFZ). A critical review of reports from the time has allowed us to discredit the claims of the earthquake's effects quite far away from the epicenter. Thanks to this the magnitude remains within moderate limits. On the other hand, the study of the earthquake's effects outside Portugal and the consideration of geological factors have allowed us to produce a reliable isoseismal map. Study of this historical earthquake may greatly influence the design of structures in the rapidly developing area of the Tagus estuary.