A large body of research has linked disaster exposure to adverse mental and physical health outcomes. Few studies, however, have explored the cumulative impact of exposure to multiple disasters. Participants (N = 8,366) from the National Institute of Environmental Health Sciences Gulf Long-Term Follow-Up Study were classified as having been exposed to both, either, or neither Hurricane Katrina and the Deepwater Horizon oil spill (DHOS). Participants also reported on a range of mental and physical health symptoms. Logistic regression models found that participants who were exposed to both disasters had significantly higher odds of probable generalized anxiety disorder, odds ratio (OR) = 1.72, 95% CI [1.52, 1.96]; major depression, OR = 1.53, 95% CI [1.32, 1.77]; and posttraumatic stress disorder, OR = 2.51, 95% CI [2.03, 3.10], than participants who were exposed to only one disaster, ps < .001. Additionally, a linear regression model found that participants who were exposed to both disasters had significantly more physical health symptoms at the time of the spill than those who were exposed to only one disaster, B = 0.99, SE = .20, p < .001. The results indicate that cumulative disaster exposure confers enhanced risk for adverse mental and physical health outcomes. The findings demonstrate that screening for prior exposure among disaster-affected individuals might identify those at greatest risk for adverse health outcomes.