Aims: To examine the association of elevated depressive symptoms with all-cause and cardiovascular disease (CVD) mortality and determine whether these associations differ for those with and without diabetes. Methods: We included 22,807 black and white men and women aged 45–98 years at baseline (2003–2007) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Elevated depressive symptoms were defined as a score ≥ 4 on the 4-item Centers for Epidemiologic Studies of Depression Scale. Participants were classified as having diabetes, prediabetes, or no prediabetes/diabetes based on glucose levels and diabetes medication use. All-cause mortality events were available through 2018 and adjudicated CVD mortality events were available through 2015. Results: During follow-up, there were 5383 all-cause deaths, of which 1585 were adjudicated CVD deaths. The mean survival time was lower for participants with elevated depressive symptoms than those without elevated depressive symptoms for those with diabetes, prediabetes, and no prediabetes/diabetes. In multivariable adjusted models, elevated depressive symptoms increased the risk of all-cause mortality for those with diabetes (HR = 1.15; 95% CI = 1.00–1.32), prediabetes (HR = 1.56; 95% CI = 1.28–1.91), and neither prediabetes/diabetes (HR = 1.34; 95% CI = 1.19–1.50) (p for interaction = 0.0342). Findings were similar for CVD mortality. Conclusion: Elevated depressive symptoms increased the risk of all-cause and CVD mortality among individuals with and without diabetes, with a stronger magnitude of association observed among those with prediabetes. This underscores the need for assessing depressive symptoms across the glycemic spectrum, including those with prediabetes.