Ultrasound has been widely used to nondestructively evaluate various materials, including biological tissues. Quantitative ultrasound has been used to assess bone quality and fracture risk. A pulsed phase-locked loop (PPLL) method has been proven for very sensitive tracking of ultrasound time-of-flight (TOF) changes. The objective of this work was to determine if the PPLL TOF tracking is sensitive to bone deformation changes during loading. The ability to noninvasively detect bone deformations has many implications, including assessment of bone strength and more accurate osteoporosis diagnostics and fracture risk prediction using a measure of bone mechanical quality. Fresh sheep femur cortical bone shell samples were instrumented with three 3-element rosette strain gauges and then tested under mechanical compression with eight loading levels using an MTS machine. Samples were divided into two groups based on internal marrow cavity content: with original marrow, or replaced with water. During compressive loading ultrasound waves were measured through acoustic transmission across the mid-diaphysis of bone. Finite element analysis (FEA) was used to describe ultrasound propagation path length changes under loading based on µCT-determined bone geometry. The results indicated that PPLL output correlates well to measured axial strain, with R(2) values of 0.70 ± 0.27 and 0.62 ± 0.29 for the marrow and water groups, respectively. The PPLL output correlates better with the ultrasound path length changes extracted from FEA. For the two validated FEA tests, correlation was improved to R(2) = 0.993 and R(2) = 0.879 through cortical path, from 0.815 and 0.794 via marrow path, respectively. This study shows that PPLL readings are sensitive to displacement changes during external bone loading, which may have potential to noninvasively assess bone strain and tissue mechanical properties.