Natural silicate glasses are an essential component of many volcanic rock types including coherent and pyroclastic rocks; they span a wide range of compositions, occur in diverse environments, and form under a variety of pressure-temperature conditions. In subsurface volcanic environments (e.g., conduits and feeders), melts intersect the thermodynamically defined glass transition temperature to form glasses at elevated confining pressures and under differential stresses. We present a series of room temperature experiments designed to explore the fundamental mechanical and fragmentation behavior of natural (obsidian) and synthetic glasses (Pyrex™) under confining pressures of 0.1–100 MPa. In each experiment, glass cores are driven to brittle failure under compressive triaxial stress. Analysis of the load-displacement response curves is used to quantify the storage of energy in samples prior to failure, the (brittle) release of elastic energy at failure, and the residual energy stored in the post-failure material. We then establish a relationship between the energy density within the sample at failure and the grain-size distributions (D-values) of the experimental products. The relationship between D-values and energy density for compressive fragmentation is significantly different from relationships established by previous workers for decompressive fragmentation. Compressive fragmentation is found to have lower fragmentation efficiency than fragmentation through decompression (i.e., a smaller change in D-value with increasing energy density). We further show that the stress storage capacity of natural glasses can be enhanced (approaching synthetic glasses) through heat treatment.