African Americans face unique higher and lower risks for gastroenterological health conditions compared to other racial groups in the USA. Genetic predispositions and levels of African admixture underscore the varied prevalence of these diseases. They show higher rates of hepatitis infections but are less often screened or referred for specialty care. Despite the availability of effective treatments, disparities in treatment accessibility and outcomes continue. Certain conditions, such as gallbladder disease and Barrett’s esophagus, have a lower incidence in this population, while they bear a greater burden of Helicobacter pylori. Factors like genetic predispositions, socioeconomic status, and healthcare access contribute to these health disparities, emphasizing the need for tailored medical strategies to enhance healthcare outcomes for African Americans.