Perceived work ability refers to a worker’s assessment of his or her ability to continue working in his or her job, given characteristics of the job along with his or her personal resources. Perceived work ability is a critical variable to study in the U.S., given an aging workforce, trends to delay retirement, and U.S. policy considerations to delay the age at which full Social Security retirement benefits may be obtained. Based on the Job Demands-Resources Model, cognitive appraisal theory of stress and push/pull factors related to retirement, we proposed and tested a conceptual model of antecedents and outcomes of perceived work ability using three independent samples of U.S. working adults. Data regarding workers’ job characteristics were from self-report and O*NET measures. Results from relative importance analysis indicated that health and sense of control were consistently and most strongly related to work ability perceptions relative to other job demands and job resources when perceived work ability was measured concurrently or two weeks later in samples with varying occupations. Job demands (along with health and sense of control) were most strongly related to work ability perceptions when perceived work ability was measured in a manufacturing worker sample 1.6 years later. Perceived work ability also predicted lagged labor force outcomes (absence, retirement, and disability leave) while controlling for other known predictors of each. Consistent indirect effects were observed from health status and sense of control to all three of these outcomes via perceived work ability.