Understanding the mechanical properties of trabecular bone within the metaphysis of the proximal humerus is becoming increasingly important for the design of humeral head joint replacement components that prioritize bone preservation. The aim of this study was to perform full-field mechanical testing methods on isolated trabecular bone cores from the humeral head to experimentally measure the local magnitude of strain before macroscopic failure and to characterize the ultimate strength of each core. Isolated cubic trabecular bone cores were extracted from the center of humeral head osteotomies retrieved from (1) patients with end-stage osteoarthritis (OA) undergoing total shoulder arthroplasty (TSA) and (2) normal nonpathologic cadaveric humeral heads. A custom computed tomography (CT)-compatible loading device was used to perform compressive mechanical testing. For 10 of the OA specimens, stepwise loading was performed directly within a microCT scanner and digital volume correlation (DVC) was used to measure full-field strains throughout the trabecular structure. A higher variability in ultimate strength was measured for the trabecular cores retrieved from OA humeral heads (range:​ 2.8–7.6 MPa) compared to the normal cadaveric humeral heads (range:​ 2.2–5.4 MPa), but no statistically significant difference between the groups was found (p = 0.06). Ultimate strength was strongly correlated with bone volume fraction (OA r² = 0.72;​ normal r² = 0.76) and bone mineral content (OA r² = 0.79;​ normal r² = 0.77). At the trabecular level, 95th percentile of third principal strains, measured at a subvolume size of 152 µm, exceeded 19,000 µε for each of the 10 specimens (range:​ −19,551 to −36,535 µε) before macroscopic failure of the cores occured. No strong linear correlations (r² ≥ 0.50) were found between the median or 95th percentile of DVC third principal strain and the corresponding morphometric parameters of each individual bone core. The results of this study indicate that bone volume fraction and bone mineral content heavily influence the apparent ultimate strength of trabecular bone cores collected from OA patients undergoing TSA. Clinical significance:​ The strong correlations observed within this study further emphasize the importance of considering bone mineral content or bone volume fraction measurements in assessing the localized risk of trabecular bone fracture for orthopedic applications.