The evolution and function of the mammalian skull and feeding apparatus is intimately related to the mechanical demands imposed by food items. The effect of dietary properties on craniofacial form has long been the focus of numerous functional, developmental, and paleontological studies, with increasing work dedicated to the importance of phenotypic plasticity. As bone is a dynamic tissue capable of sensing and responding to mechanical loads, morphological variation related to differential loading is well established for many masticatory elements. While more mechanically challenging diets have been shown to result in greater jaw proportions, it remains poorly understand how long-term dietary variability affects the adaptive osteogenic response of multiple cranial sites at multiple levels of bony organization. This is a significant oversight given the diverse functional requirements of a hierarchically organized, morphologically complex structure like the skull.This experimental research evaluated the effects of long-term differential loading on the macro-, micro-, and nanoscale responses of bone at a series of cranial sites. Sites were chosen to represent regions involved in mastication (i.e., jaws) as well as those less directly involved (i.e., neurocranium). It was hypothesized that masticatory regions would exhibit a more pronounced response to elevated loading and that cortical bone quantity and quality would be positively related to diet-induced loading levels in masticatory elements.Results indicate that diet-induced differences in loading influences plasticity in masticatory elements without corresponding changes in the neurocranium, suggesting regional variation in response to mechanical forces. More specifically, the presence and magnitude of bone adaptation varied according to the level of analysis. This is critically important as it suggests that physiological adaptation, and corresponding variation in skeletal performance, may reside differentially at one level of bony architecture, thus potentially affecting accurate behavioral reconstructions. It also emphasizes the limitations of external metrics while underscoring the significance of considering finer levels of bone architecture with the goal of improving the accuracy of adaptive interpretations as it relates to the evolution of craniofacial form. More broadly, findings highlight functional and developmental variation in determinants of morphological integration in the skull, information of utility for ecomorphological, paleobiological, and evolutionary research.