BACKGROUND:On average, a person living in San Francisco can expect to live 83 years. This number conceals significant variation by sex, race, and place of residence. We examined deaths and area-based social factors by San Francisco neighborhood, hypothesizing that socially disadvantaged neighborhoods shoulder a disproportionate mortality burden across generations, especially deaths attributable to violence and chronic disease. These data will inform targeted interventions and guide further research into effective solutions for San Francisco’s marginalized communities.STUDY DESIGN:The San Francisco Department of Public Health provided data for the 2010–2014 top 20 causes of premature death by San Francisco neighborhood. Population-level demographic data were obtained from the US American Community Survey 2015 5-year estimate (2011–2015). The primary outcome was the association between years of life loss (YLL) and adjusted years of life lost (AYLL) for the top 20 causes of death in San Francisco and select social factors by neighborhood via linear regression analysis and heatmaps.RESULTS:The top 20 causes accounted for N = 15,687 San Francisco resident deaths from 2010–2014. Eight neighborhoods (21.0%) accounted for 47.9% of city-wide YLLs, with 6 falling below the city-wide median household income and many having a higher percent population Black, and lower education and higher unemployment levels. For chronic diseases and homicides, AYLLs increased as a neighborhood’s percent Black, below poverty level, unemployment, and below high school education increased.CONCLUSIONS:Our study highlights the mortality inequity burdening socially disadvantaged San Francisco neighborhoods, which align with areas subjected to historical discriminatory policies like redlining. These data emphasize the need to address past injustices and move toward equal access to wealth and health for all San Franciscans.