Osteogenesis imperfecta (OI) is a relatively common rare bone disease which presents with skeletal deformities and increased fracture incidence. Limited studies have characterized the properties of OI bone, which remains an obstacle in accurately predicting risk of fracture in children with OI during daily activities. To evaluate differences between OI types I, III, IV, VI, VII, and VIII, anisotropic mechanical properties were characterized during three-point bending for 299 OI and 83 control miniature cortical bone beams. Elastic modulus, yield strength, and flexural strength demonstrated anisotropy within most OI groups and controls, with significantly greater properties observed in the longitudinal orientation than transverse orientation (p ≤ 0.005). Compared to controls, OI groups resulted in significantly lower longitudinal elastic modulus and yield strength (p ≤ 0.004) except for OI type VI (p ≥ 0.14). Flexural strength was significantly lower in all OI groups compared to controls for longitudinal beams (p ≤ 0.001). Although classified as moderate to severe, the single specimen OI type VII bone resulted in the lowest elastic modulus values for both orientations and lowest yield strength and flexural strength in the transverse orientation compared to the other OI types. This study was the first to characterize mechanical properties for moderate to severe OI types VI and VII and encompassed larger sample sizes of type I, III, IV, and VIII OI bone samples to perform robust statistical analyses.