Globular clusters (GCs) are dense, gravitationally bound systems of thousands to millions of stars. They are preferentially associated with the oldest components of galaxies, so measurements of their composition can constrain the build-up of chemical elements in galaxies during the early Universe.We report a massive GC in the Andromeda Galaxy (M31), RBC EXT8, that is extremely depleted in heavy elements. Its iron abundance is about 1/800 that of the Sun and about one-third that of the most iron-poor GCs previously known. It is also strongly depleted in magnesium. These measurements challenge the notion of a metallicity floor for GCs and theoretical expectations that massive GCs could not have formed at such low metallicities.