To assess the associations of docosahexaenoic acid (DHA), a marine omega-3 fatty acid, with long-term all-cause mortality, cardiovascular (CV) mortality, and cancer mortality. We analyzed data from UK Biobank, which included 117,702 subjects with baseline plasma DHA levels and 12.7 years of follow-up between April 2007 and December 2021. Associations with risk for mortality endpoints were analyzed categorically by quintile of DHA plasma levels. Comparing the lowest to highest quintiles of circulating levels of DHA, there was 21% lower risk of all-cause mortality (HR, 0.79; 95% CI, 0.74 to 0.85; P<.0001). In a secondary analysis, we merged the UK Biobank findings with those from a recent FORCE (Fatty Acid and Outcome Research Consortium) meta-analysis that included 17 prospective cohort studies and 42,702 individuals examining DHA and mortality associations. The cumulative sample population included 160,404 individuals and 24,342 deaths during a median of 14 years of follow-up. After multivariable adjustment for relevant risk factors comparing the lowest to the highest quintiles of DHA, there was 17% lower risk of all-cause mortality (95% CI, 0.79 to 0.87; P<.0001), 21% lower risk for CV disease mortality (95% CI, 0.73 to 0.87; P<.001), 17% lower risk for cancer mortality (95% CI, 0.77 to 0.89; P<.0001), and 15% lower risk for all other mortality (95% CI, 0.79 to 0.91; P<.001). Higher DHA levels were associated with significant risk reductions in all-cause mortality, as well as reduced risks for deaths due to CV disease, cancer, and all other causes. The findings strengthen the hypothesis that DHA, a marine-sourced omega-3, may support CV health and lifespan.