The Late Devonian was a protracted period of low speciation resulting in biodiversity decline, culminating in extinction events near the Devonian–Carboniferous boundary. Recent evidence indicates that the final extinction event may have coincided with a dramatic drop in stratospheric ozone, possibly due to a global temperature rise. Here we study an alternative possible cause for the postulated ozone drop: a nearby supernova explosion that could inflict damage by accelerating cosmic rays that can deliver ionizing radiation for up to ∼ 100 ky. We therefore propose that the end-Devonian extinctions were triggered by supernova explosions at ∼ 20 pc, somewhat beyond the “kill distance” that would have precipitated a full mass extinction. Such nearby supernovae are likely due to core collapses of massive stars; these are concentrated in the thin Galactic disk where the Sun resides. Detecting either of the long-lived radioisotopes 146Sm or 244Pu in one or more end-Devonian extinction strata would confirm a supernova origin, point to the core-collapse explosion of a massive star, and probe supernova nucleosynthesis. Other possible tests of the supernova hypothesis are discussed.