Prior attempts to identify factors associated with physical function (here, major lower body movements) among African Americans have been constrained by a narrow range of measures, small sample sizes, or both. The 1992 Health and Retirement Study (HRS) contains a substantial over-sample of African Americans (649 men and 957 women self-respondents aged 51 to 61 years), and detailed measures of high-risk behaviors, disease prevalence and severity, impairment, and physical function. We extend the natural history of disease to the natural history of functional status and model sociodemographic characteristics, high-risk behaviors, disease prevalence and severity, and impairments as direct and indirect influences on physical function in this African American sample. This natural history of functional status model fits the data well for both men (ROC = .88) and women (ROC = .83), although there are gender differences. Slightly over one-half of the women report some difficulty in physical function, compared with one-third of the men. Women also have a higher mean body-mass and report a greater prevalence and severity in 6 of 9 chronic diseases and more pain, but are less likely to smoke or abuse alcohol than men. Importantly, many of the factors with the largest direct and indirect associations with difficulty in physical function among these African American men (alcohol abuse, smoking, body mass, diabetes, heart disease, cerebrovascular disease, arthritis, and pain) and women (alcohol abuse, body mass, arthritis, and respiratory illness) are all potentially preventable or manageable.