Background: Cancer incidence and mortality rates in the United States are declining, but this decrease may not be observed in rural areas where residents are more likely to live in poverty, smoke, and forego cancer screening. However, there is limited research exploring national rural-urban differences in cancer incidence and trends. Methods: We analyzed data from the North American Association of Central Cancer Registries' public use dataset, which includespopulation-based cancer incidence data from46 states. We calculated age-adjusted incidence rates, rate ratios, and annualpercentagechange( APC) for: Allcancers combined, selected individual cancers, and cancers associated with tobacco use and human papillomavirus (HPV). Rural-urban comparisons were made by demographic, geographic, and socioeconomic characteristicsfor2009to2013. Trendswereanalyzedfor1995to2013. Results: Combined cancers incidence rates were generally higher in urban populations, except for the South, although the urban decline in incidence rate was greater than in rural populations (10.2% vs. 4.8%, respectively). Rural cancer disparities included higher rates of tobacco-associated, HPV-associated, lung and bronchus, cervical, and colorectal cancers across most population groups. Furthermore, HPVassociated cancer incidence rates increased in rural areas (APC = 0.724, P < 0.05), while temporal trends remained stable in urban areas. Conclusions: Cancer rates associated with modifiable risks-tobacco, HPV, and some preventive screening modalities (e.g., colorectal and cervical cancers)-were higher in rural compared with urban populations. Impact: Population-based, clinical, and/or policy strategies and interventions that address these modifiable risk factors could help reduce cancer disparities experienced in rural populations.