Experimental investigations for anatomic variation in the magnitude and anisotropy of elastic constants in human femoral cortical bone tissue have typically focused on a limited number of convenient sites near the mid-diaphysis. However, the proximal and distal ends of the diaphysis are more clinically relevant to common orthopaedic procedures and interesting mechanobiology. Therefore, the objective of this study was to measure anatomic variation in the elastic anisotropy and inhomogeneity of human cortical bone tissue along the entire length (15%–85% of the total femur length), and around the periphery (anterior, medial, posterior and lateral quadrants) of the femoral diaphysis, using ultrasonic wave propagation in the three orthogonal specimen axes. The elastic symmetry of tissue in the distal and extreme proximal portions of the diaphysis (15%–45% and 75%–85% of the total femur length, respectively) was, at most, orthotropic. In contrast, the elastic symmetry of tissue near the mid- and proximal mid-diaphysis (50%–70% of the total femur length) was reasonably approximated as transversely isotropic. The magnitudes of elastic constants generally reached maxima near the mid- and proximal mid-diaphysis in the lateral and medial quadrants, and decreased toward the epiphyses, as well as the posterior and anterior quadrants. The elastic anisotropy ratio in the longitudinal and radial anatomic axes showed the opposite trends. These variations were significantly correlated with the apparent tissue density, as expected. In summary, the human femur exhibited statistically significant anatomic variation in elastic anisotropy, which may have important implications for whole bone numerical models and mechanobiology.