This study examined trends in rural-urban disparities in all-cause and cause-specific mortality in the USA between 1969 and 2009. A rural-urban continuum measure was linked to county-level mortality data. Age-adjusted death rates were calculated by sex, race, cause-of-death, area-poverty, and urbanization level for 13 time periods between 1969 and 2009. Cause-of-death decomposition and log-linear and Poisson regression were used to analyze rural-urban differentials. Mortality rates increased with increasing levels of rurality overall and for non-Hispanic whites, blacks, and American Indians/Alaska Natives. Despite the declining mortality trends, mortality risks for both males and females and for blacks and whites have been increasingly higher in non-metropolitan than metropolitan areas, particularly since 1990. In 2005-2009, mortality rates varied from 391.9 per 100,000 population for Asians/Pacific Islanders in rural areas to 1,063.2 for blacks in small-urban towns. Poverty gradients were steeper in rural areas, which maintained higher mortality than urban areas after adjustment for poverty level. Poor blacks in non-metropolitan areas experienced two to three times higher all-cause and premature mortality risks than affluent blacks and whites in metropolitan areas. Disparities widened over time; excess mortality from all causes combined and from several major causes of death in non-metropolitan areas was greater in 2005-2009 than in 1990-1992. Causes of death contributing most to the increasing rural-urban disparity and higher rural mortality include heart disease, unintentional injuries, COPD, lung cancer, stroke, suicide, diabetes, nephritis, pneumonia/influenza, cirrhosis, and Alzheimer's disease. Residents in metropolitan areas experienced larger mortality reductions during the past four decades than non-metropolitan residents, contributing to the widening gap.