Research in applied psychology has found that job demands affect employee health outcomes. However, less is known about the mechanisms linking job demands to more distal health outcomes, such as death, and how other job characteristics (i.e., job control) and individual differences (i.e., cognitive ability) might buffer these relationships. Accordingly, we drew from theories from the work stress and medical literatures to argue that job control and cognitive ability moderate the positive relationship between job demands and the probability of mortality, via the mediating effects of poor physical (i.e., allostatic load) and mental health (i.e., depression) indicators. We tested our hypotheses using a 20-year time-lagged design in a sample of 3,148 individuals with mental health data (and a subsample of 754 with physical health data) from the Midlife in the United States Survey. We found that job control and cognitive ability buffered the positive relationship between job demands and poor mental health. Unexpectedly, we found that job control, but not cognitive ability, moderated the relationship between job demands and physical health, such that job demands were related to better physical health under conditions of high control, and unrelated to physical health under conditions of low control. In turn, physical and mental health mediated the moderated (by job control and cognitive ability) job demands-mortality relationship. Our findings suggest that job demands relate to death differentially via physical and mental health, and that these relationships are bounded in unique ways by job control and cognitive ability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).