The ability to simultaneously process and integrate multiple sensory stimuli is paramount to effective daily function and essential for normal cognition. Multisensory management depends critically on the interplay between bottom-up and top-down processing of sensory information, with white matter (WM) tracts acting as the conduit between cortical and subcortical gray matter (GM) regions. White matter tracts and GM structures operate in concert to manage both multisensory signals and cognition. Altered sensory processing leads to difficulties in reweighting and modulating multisensory input during various routine environmental challenges, and thus contributes to cognitive dysfunction. To examine the specific role of WM in altered sensory processing and cognitive dysfunction, this review focuses on two neurologic disorders with diffuse WM pathology, multiple sclerosis and mild traumatic brain injury, in which persistently altered sensory processing and cognitive impairment are common. In these disorders, cognitive dysfunction in association with altered sensory processing may develop initially from slowed signaling in WM tracts and, in some cases, GM pathology secondary to WM disruption, but also because of interference with cognitive function by the added burden of managing concurrent multimodal primary sensory signals. These insights promise to inform research in the neuroimaging, clinical assessment, and treatment of WM disorders, and the investigation of WM-behavior relationships.