A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.