The burden of noncommunicable diseases and social inequalities in health among urban populations is becoming a common problem around the world. This phenomenon is further compounded by population aging. Japan faces the task of maintaining its high level of population health while dealing with these challenges. This study focused on the ten largest cities in Japan and, using publicly available administrative data, analyzed standardized mortality ratios to examine inequalities in relative mortality levels due to major noncommunicable disease at both city and subcity levels. On average, the ten major cities had excess mortality due to cancer and lower mortality due to heart disease and cerebrovascular disease compared to the country as a whole. Substantial inequalities in relative mortality were observed both between and within cities, especially for heart disease and cerebrovascular disease among men. Inequalities in relative mortality levels within cities appear to be increasing over time even while relative mortality levels are decreasing overall. The widely observed health inequalities signal the need for actions to ensure health equity while addressing the burden of noncommunicable diseases. Increasingly, more countries will have to deal with these challenges of inequity, urbanization, aging, and noncommunicable diseases. Local health governance informed by locally specific data on health determinants and outcomes is essential for developing contextualized interventions to improve health and health equity in major urban areas.