Background: Leg pain, especially of the knees and hips, is common among senior workers and may limit the ability to perform physically demanding work. In light of the aging workforce, this study determined the joint association of physical work demands and leg pain intensity for work-limiting pain in senior workers. Methods: Currently employed senior workers (≥50 years) participated in the SeniorWorkingLife study in 2018 (n = 12,879). Associations between the combination of physical work demands and leg pain intensity (interaction) with work-limiting pain (outcome) were modeled using binary logistic regression analyses while controlling for potential covariates. Results: We found a significant interaction (P < 0.001) between physical work demands and leg pain intensity for work-limiting pain. The combination of higher physical work demands and higher leg pain intensity had the worst outcome in terms of the odds of experiencing work-limiting pain. For example, 70% of those with the combination of high physical work demands and leg pain intensity ≥7 (scale 0–10) experienced that the pain limited them to at least some degree in their work. Conclusions: The combination of high physical work demands and high leg pain intensity are associated with limited ability to perform work among senior workers. These findings highlight the importance of prioritizing the physical work environment in physically demanding occupations, particularly among senior workers, for prolonging working life. Thus, adjusting the work demands, e.g. through use of assistive devices, and lowering the pain, e.g. through physical rehabilitation, may be necessary to sustain work ability to a high age in this group of workers. Trial registration: This was registered as a cohort study in ClinicalTrials.gov (Identifier: NCT03634410) on the 18th of August 2018 (Retrospectively registered).