BACKGROUND: Although cardiovascular mortality (CVM) rates in the United States have been declining overall, our study evaluated whether this holds true for areas with increased social deprivation. METHODS AND RESULTS: We used county-level cross-sectional age-adjusted CVM rates (aa-CVM) (2000–2019) linked to the Centers for Disease Control and Prevention Social Vulnerability Index (SVI–2010). We grouped counties as per SVI (Groups I 0– 0.2, II 0.21– 0.4, III 0.41– 0.6, IV 0.61– 0.8, and V 0.81–1) and calculated the relative change in the aa-CVM between 2000 to 2003 and 2016 to 2019. We used adjusted linear regression analyses to explore the association between a higher SVI and temporal aa-CVM improvement; we studied this temporal change in aa-CVM across subgroups of race, sex, and location. The median aa-CVM rate (per 100 000) was 272.6 (interquartile range [IQR]: 237.5– 311.7). The aa-CVM was higher in men (315.6 [IQR: 273.4– 363.9]) than women (221.3 [IQR: 189.6–256.7]), and in Black residents (347.2 [IQR: 301.1– 391.1]; P<0.001) than White residents (258.9 [IQR: 226–299.1]; P<0.001). The aa-CVM for SVI I (233.6 [IQR: 214.8–257.0]) was significantly lower than that of group V (323.6 [IQR: 277.2– 359.2]; P<0.001). The relative reduction in CVM was significantly higher for SVI group I (32.2% [IQR: 24.2– 38.4]) than group V (27.2% [IQR: 19– 34.1]) counties. After multivariable adjustment, a higher SVI index was associated with lower relative improvement in the age-adjusted CVM (model coefficient −3.11 [95% CI, −5.66 to −1.22]; P<0.001). CONCLUSIONS: Socially deprived counties in the United States had higher aa-CVM rates, and the improvement in aa-CVM over the past 20 years was lower in these counties.