On 4 May 1910, the most destructive earthquake in the history of Costa Rica (Ms 6.4) destroyed the city of Cartago, a major city located in the Valle Central of Costa Rica. Using both palaeo-seismological and morphotectonic analyses, we have found evidence that points to the Aguacaliente Fault (AF) as the source of this earthquake. This structure is a N100° E trending, strike-slip fault situated to the south of Cartago and within a wide band of deformation. We excavated two trenches near Bermejo, south of Cartago. We found evidence of three surface ruptures within the last 1000 years on this fault. The age of the most recent rupture is consistent with the Cartago 1910 earthquake. The AF is a seismogenic source capable of producing large earthquakes (Mw 6.5–6.9) with an estimated recurrence interval of about 500 years.