Background: Biomechanical analysis of human mandible is important not only to understand mechanical behavior and structural properties, but also to diagnose and develop treatment options for mandibular disorders. Therefore, the objective of this research was to generate analytical and experimental data on mandibles, construct custom 3D models, and compare the analytically derived maximum strains with strain gage data in five areas of interest for each mandible. Methods: We investigated the surface strains in the cadaveric human mandibles under different configurations of cyclic compressive loads in an experimental setting and compared these experimental strain data with results derived from computational finite element analysis (FEA), accurately replicating the experiments. Strains on the surface of each mandible were measured with strain gauges, and subsequently a subject-specific finite element (FE) volume mesh was generated from computed tomography (CT) scans of each mandible. Strain patterns of each mandible were derived from the FEA simulating the experimental setup and matched with the experimental data. Findings: Analysis of experimental data showed that strain as measured at the condylar locations was significantly different from those at other locations on the mandible, and that the sex and age of the subject did not have a significant correlation with the strain. Comparing the FE numerical predictions with the experimental data, we found a good statistical correlation and statistical agreement between in-vitro measurements and FE results. Interpretation: The study demonstrates that our methodology of generating subject-specific FE models is a valid and accurate, non-invasive method to evaluate the complex biomechanical behavior of human mandibles.