Recently, the United States experienced its first resurgence of major amputations in more than 20 years. Compounding this rise is a longstanding history of disparities. Patients identifying as non-Hispanic Black are twice as likely to lose a limb as those identifying as non-Hispanic White. Those identifying as Latino face a 30% increase. Rural patients are also more likely to undergo major amputations, and the rural-urban disparity is widening. We used the National Institute on Minority Health and Health Disparities framework to better understand these disparities and identify common factors contributing to them. Common factors were abundant and included increased prevalence of diabetes, possible lower rates of foot self-care, transportation barriers to medical appointments, living in disadvantaged neighborhoods, and lack of insurance. Solutions within and outside the health care realm are needed. Health care-specific interventions that embed preventative and ambulatory care services within communities may be particularly high yield.