ImportanceUS rural vs nonrural populations have striking disparities in diabetes care. Whether rurality contributes to disparities in diabetes mortality is unknown.ObjectiveTo examine rates and trends in diabetes mortality based on county urbanization.Design, Setting, and ParticipantsIn this observational, cross-sectional study, the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database was searched from January 1, 1999, to December 31, 2018, for diabetes as a multiple cause and the underlying cause of death among residents aged 25 years or older in US counties. County urbanization was categorized as metro, medium-small, and rural. Weighted multiple linear regression models and jackknife resampling, with a 3-segment time component, were used. The models included exposures with up to 3-way interactions and were age standardized to the 2009-2010 population. The analyses were conducted from July 1, 2020, to February 1, 2022.ExposuresCounty urbanization (metro, medium-small, or rural), gender (men or women), age group (25-54, 55-74, or ≥75 years), and region (Midwest, Northeast, South, or West).Main Outcomes and MeasuresAnnual diabetes mortality rate per 100 000 people.ResultsFrom 1999-2018, based on 4 022 238 309 person-years, diabetes was a multiple cause of death for 4 735 849 adults aged 25 years or older. As a multiple cause, diabetes mortality rates in 2017-2018 vs 1999-2000 were highest and unchanged in rural counties (157.2 [95% CI, 150.7-163.7] vs 154.1 [95% CI, 148.2-160.1]; P = .49) but lower in medium-small counties (123.6 [95% CI, 119.6-127.6] vs 133.6 [95% CI, 128.4-138.8]; P = .003) and urban counties (92.9 [95% CI, 90.5-95.3] vs 109.7 [95% CI, 105.2-114.1]; P < .001). In 2017-2018 vs 1999-2000, mortality rates were higher in rural men (+18.2; 95% CI, 14.3-22.1) but lower in rural women (−14.0; 95% CI, −17.7 to −10.3) (P < .001 for both). In the 25- to 54-year age group, mortality rates in 2017-2018 vs 1999-2000 showed a greater increase in rural counties (+9.4; 95% CI, 8.6-10.2) compared with medium-small counties (+4.5; 95% CI, 4.0-5.0) and metro counties (+0.9; 95% CI, 0.4-1.4) (P < .001 for all). Of all regions and urbanization levels, the mortality rate in 2017-2018 vs 1999-2000 was higher only in the rural South (+13.8; 95% CI, 7.6-20.0; P < .001).Conclusions and RelevanceIn this cross-sectional study, US rural counties had the highest overall diabetes mortality rate. The determinants of persistent rural disparities, in particular for rural men and for adults in the rural South, require investigation.