Chronic pain (CP) significantly impacts quality of life and increases noncommunicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing diabetes, depression, and hypertension. International studies suggest higher mortality in CP populations, yet prior U.S. data are inconclusive. To investigate CP's mortality risk, we analyzed National Health Interview Survey and National Death Index data. We hypothesized that individuals with CP and high-impact CP (HICP [≥1 activity limitation]) would exhibit higher mortality rates. National Health Interview Survey provided demographics, pain reporting, lifestyle, and psychosocial data matched with National Death Index mortality records. Chi-square analyses explored the relationships between CP/HICP and demographics, lifestyle factors, psychosocial variables, and mortality. Cox proportional hazards models assessed mortality risk between groups. The weighted sample was 245,899,776; 20% reported CP and 8% HICP, both groups exhibiting higher mortality rates than pain-free individuals (CP: 5.55%, HICP: 8.79%, total: 2.82%). Hazard ratios indicated nearly double the mortality risk for CP and 2.5 times higher risk for HICP compared to those without these conditions. Adjusting for lifestyle and psychosocial factors reduced mortality risk but remained elevated compared with non-CP individuals. Heart disease, malignant neoplasms, and chronic lower respiratory diseases accounted for a higher percentage of deaths in CP cases. CP individuals showed higher rates of smoking, alcohol consumption, obesity, inactivity, depression, anxiety, emotional problems, and sleep disturbances. CP and HICP significantly influence mortality outcomes, leading to excess deaths compared with pain-free individuals. Given the relationship between pain, lifestyle, psychosocial variables, and mortality, further investigations are needed into CP causation and prevention strategies. PerspectiveThis article presents evidence regarding the relationship between CP, HICP, and mortality. Additional findings are discussed regarding the impact of demographics, lifestyle, and psychosocial variables on mortality in those with versus without CP and HICP. These findings are crucial for informing future research, prevention, and healthcare management strategies.