The cancer landscape of the USA is continually evolving owing to changing risk factor patterns and disease classifications, improvements in detection and treatment, and demographic changes, such as ageing and population growth. Monitoring the burden of cancer, including incidence and mortality, is a key tool for assessing progress, identifying emerging trends and setting priorities to reduce the burden. In this Perspective, we describe trends in cancer incidence and mortality in the USA overall, and for major cancer types, and describe the main contributing factors, including risk factors, screening, treatment and access to care. When relevant, we provide information based on sex and common classifications of race/ethnicity, socioeconomic status and geographical region. We then discuss the implications of the patterns of cancer incidence and mortality for cancer research, prevention and care.