Physical activity (PA) may be considered an alternative method to ameliorate the elevated mortality risks associated with cadmium exposure. In this prospective cohort study, a total of 20,253 participants (weighted mean age, 47.79 years), including 10,247 men (weighted prevalence: 50.1 %), aged 18 years or older, were selected from the National Health and Nutrition Examination Survey from 2007 to 2018. Multivariable Cox proportional hazards regression models were utilized to evaluate the associations between blood cadmium levels, PA, and the risks of mortality. Restricted cubic spline analyses were employed to investigate the nonlinear relationships between blood cadmium and PA levels and mortality risks. During a median follow-up of 7.6 years, a total of 2002 (9.89 %) all-cause deaths occurred, of which 581 (2.87 %) participants were due to cardiovascular disease (CVD) and 498 (2.46 %) died of cancer. J-shaped associations were observed for blood cadmium with risks of mortality (all P