Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Using accelerometer-based measures, we 1) described the mortality dose-response for sedentary time and light- and moderate-to-vigorous-intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. US adults (n = 4840) from NHANES (2003-2006) wore an accelerometer for ≤7 d and were followed prospectively for mortality. Proportional hazards models were used to estimate adjusted HRs and 95% CIs for mortality associations with time spent sedentary and in light- and moderate-to-vigorous-intensity physical activity. Splines were used to graphically present behavior-mortality relation. Isotemporal models estimated replacement associations for sedentary time, and separate models were fit for low- (<5.8 h total activity/d) and high-active participants to account for nonlinear associations. Over a mean of 6.6 y, 700 deaths occurred. Compared with less-sedentary adults (6 sedentary h/d), those who spent 10 sedentary h/d had 29% greater risk (HR: 1.29; 95% CI: 1.1, 1.5). Compared with those who did less light activity (3 h/d), those who did 5 h of light activity/d had 23% lower risk (HR: 0.77; 95% CI: 0.6, 1.0). There was no association with mortality for sedentary time or light or moderate-to-vigorous activity in highly active adults. In less-active adults, replacing 1 h of sedentary time with either light- or moderate-to-vigorous-intensity activity was associated with 18% and 42% lower mortality, respectively. Health promotion efforts for physical activity have mostly focused on moderate-to-vigorous activity. However, our findings derived from accelerometer-based measurements suggest that increasing light-intensity activity and reducing sedentary time are also important, particularly for inactive adults.