White matter hyperintensities (WMH) are a common finding on T2-weighted FLAIR MRI and often exhibit distinct spatial patterns depending on underlying disease mechanism. Although WMH are frequently observed as part of normal aging, their prevalence and burden increase with neurodegneration. WMH are typically classified based on anatomical location into periventricular (PVWMH) and deep (DWMH), with lesion formation location reflecting differences in underlying pathophysiology. PVWMH are believed to be closely linked to ventricular enlargement and age-related brain atrophy. As the ventricular wall expand, the ependymal lining becomes stretched, compromising its barrier functionality. This process allows cerebrospinal fluid (CSF) leak into adjacent periventricular white matter, leading to tissue damage and lesion formation. In contrast, DWMH are more commonly associated with vascular pathology or traumatic mechanisms rather than CSF-mediated processes. In the context of repetitive head impacts, damage is thought to arise from cumulative mechanical strain within deep white matter tracts. Despite their clinical importance, the mechanisms governing where WMH originate and how they evolve over time remain poorly understood. Here, we present a mechanics based computational model to define WMH formation in (1) age-related periventricular WMH and (2) sports-related deep WMH. We use functional loading derived from brain deformation to trigger damage, coupled with a reaction–diffusion model to govern subsequent lesion growth. In the aging scenario, ventricular wall deformation serves as the mechanical trigger for damage, whereas in the context of repetitive head impacts, impact-induced deformation at the gray–white matter interface is used to initiate damage. Collectively, our findings show that mechanically driven damage, coupled with reaction–diffusion growth, can reproduce distinct periventricular and deep WMH patterns consistent with observed imaging patterns.