We investigate the rate-dependent compressive failure and fragmentation of a hot-pressed boron carbide, under both uniaxial and confined biaxial compression, using quantitative fragment analysis coupled with quantitative microstructural analysis. Two distinct fragmentation regimes are observed, one of which appears to be more sensitive to the microstructural length scales in the material, while the second is more sensitive to the structural character and boundary conditions of the compressed sample. The first regime, which we refer to as microstructure-dependent, appears to be associated with smaller fragments arising from the coalescence of fractures initiating from graphitic inclusions. This regime appears to become more dominant as the strain rate is increased and as the stress-state becomes more confined. The second regime generates larger fragments with the resulting fragment size distribution dependent on the specific structural mechanisms that are activated during macroscopic failure (e.g., buckling of local columns developed during the compression). The average fragment size in the latter regime appears to be reasonably predicted by current fragmentation models. This improved understanding of the effects of microstructure and confinement on fragmentation then provides new insights into prior ballistic studies involving boron carbide.