The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71–0.85) and 0.79 (0.71–0.86) for all-cause mortality, 0.59 (0.48–0.72) and 0.69 (0.56–0.85) for CVD mortality, and 0.68 (0.56–0.84) and 0.73 (0.60–0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78–0.95) and 0.88 (0.80–0.97) for all-cause mortality and 0.53 (0.41–0.69) and 0.56 (0.44–0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults.