Many complications in craniofacial surgery can be attributed to a lack of characterization of facial skeletal strain patterns. This study aimed to delineate human midfacial strain patterns under uniform muscle loading. The left sides of 5 fresh-frozen human cadaveric heads were dissected of all soft tissues except the temporalis and masseter muscles. Tensile forces were applied to the free mandibular ends of the muscles. Maxillary alveolar arches were used to restrain the skulls. Eight strain gauges were bonded to the surface of the midface to measure the strain under single muscle loading conditions (100 N). Maxillary strain gauges revealed a biaxial load state for both muscles. Thin antral bone experienced high maximum principal tensile strains (maximum of 685.5 με) and high minimum principal compressive strains (maximum of -722.44 με). Similar biaxial patterns of lower magnitude were measured on the zygoma (maximum of 208.59 με for maximum principal strains and -78.11 με for minimum principal strains). Results, consistent for all specimens and counter to previously accepted concepts of biomechanical behavior of the midface under masticatory muscle loading, included high strain in the thin maxillary antral wall, rotational bending through the maxilla and zygoma, and a previously underestimated contribution of the temporalis muscle. This experimental model produced repeatable strain patterns quantifying the mechanics of the facial skeleton. These new counterintuitive findings underscore the need for accurate characterization of craniofacial strain patterns to address problems in the current treatment methods and develop robust design criteria.