In this study, we quantify the seismic and tsunami hazard in the Lesser Antilles subduction zone, focusing on the plate interface offshore of Guadeloupe. We compare potential strain accumulated via GPS-derived plate motions to strain release due to earthquakes that have occurred over the past 110 yr, and compute the resulting moment deficit. Our results suggest that enough strain is currently stored in the seismogenic zone of the Lesser Antilles subduction arc in the region of Guadeloupe to cause a large and damaging earthquake of magnitude Mw ∼ 8.2 ± 0.4. We model several scenario earthquakes over this magnitude range, using a variety of earthquake magnitudes and rupture areas, and utilizing the USGS ShakeMap and PAGER software packages. Strong ground shaking during the earthquake will likely cause loss of life and damage estimated to be in the range of several tens to several hundreds of fatalities and hundreds of millions to potentially billions of U.S. dollars of damage. In addition, such an event could produce a significant tsunami. Modelled tsunamis resulting from these scenario earthquakes predict meter-scale wave amplitudes even for events at the lower end of our magnitude range (M 7.8), and heights of over 3 m in several locations with our favoured scenario (M 8.0, partially locked interface from 15–45 km depth). In all scenarios, only short lead-times (on the order of tens of minutes) would be possible in the Caribbean before the arrival of damaging waves.