he central Ionian Sea is one of the most seismogenic areas in the Mediterranean Sea region. In particular, the island of Lefkada, Greece, has experienced many catastrophic earthquakes. The historical seismicity of Lefkada has been revised by utilizing published and little-known macroseismic information sources, e.g., administrative documents, letters, marginal notes, and eyewitness accounts. We organized a new descriptive and parametric catalogue of 44 earthquakes that had their maximum macroseismic intensity in Lefkada and covered the time interval from the 15th century A.D. up to 1911. Earthquake dates, origin times, intensities, magnitudes, and epicentral coordinates were estimated or revised. Magnitudes estimated in previous catalogues in general are larger with respect to our magnitude determinations, possibly due to different calculation methods. The descriptive part of the catalogue includes descriptions of the earthquakes’ impact on buildings and of environmental effects, e.g., landslides and local tsunamis. The catalogue completeness gradually increases with time but is likely complete for the entire period examined lower magnitude threshold Mw = 6.0. One important yet puzzling earthquake is the large one that reportedly ruptured the Strait of Otranto and damaged an unprecedentedly extensive region in Italy, Albania, and Greece, including Lefkada, on 9/20 February 1743. Little-known documents revealed that the heavy destruction supposedly caused in Lefkada was very likely due to amalgamated information regarding local earthquakes and the large one.