Normal tissue toxicity is an important consideration in the continued development of more effective external beam radiotherapy (EBRT) regimens for head and neck tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity represents a crucial step in decreasing potential toxicity. To date, no imaging modality has been shown to detect changes in bone vascularity in real time during treatment. Based on our institutional experience with multi-parametric MRI, we hypothesized that DCE-MRI can provide in-treatment information regarding EBRT-induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT treatment for head and neck cancer were prospectively imaged prior to, mid-course, and following treatment. DCE-MRI scans were co-registered to dosimetric maps to correlate EBRT dose and change in mandibular bone vascularity as measured by Ktrans and Ve. DCE-MRI was able to detect dose-dependent changes in both Ktrans and Ve in a subset of patients. One patient who developed ORN during the study period demonstrated decreases in Ktrans and Ve following treatment completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can detect dose-dependent alterations in mandibular bone vascularity during chemoradiotherapy, providing biomarkers that are physiological correlates of acute of acute mandibular vascular injury and recovery temporal kinetics.