Alzheimer’s disease (AD) shows various symptoms that reflect cognitive impairment and loss of neural circuit integrity. Sensory dysfunctions such as olfactory and ocular pathology are also observed and used as indicators for early detection of AD. Although mastication is suggested to correlate with AD progression, changes in the masticatory system have yet to be established in transgenic animal models of AD. In the present study, we have assessed pathologic hallmarks of AD with the masticatory behavior of 5XFAD mice. We found that masticatory efficiency and maximum biting force were decreased in 5XFAD mice, with no significant change in general motor function. Immunohistochemical analysis revealed significant accumulation of Aβ (amyloid β), increased microglia number, and cell death in Vmo (trigeminal motor nucleus) as compared with other cranial motor nuclei that innervate the orofacial region. Masseter muscle weight and muscle fiber size were also decreased in 5XFAD mice. Taken together, our results demonstrate that Aβ accumulation in Vmo contributes to masticatory dysfunction in 5XFAD mice, suggesting a close association between masticatory dysfunction and dementia.