Introduction Studies in US Hispanic adults indicate no deleterious association between obesity and death. We tested the hypothesis that accounting for weight history would provide more insight into this nonassociation. Methods We used the National Health and Nutrition Examination Survey (NHANES) to examine associations between maximum lifetime body mass index (BMI) and all-cause and cause-specific mortality among US-residing Mexican American adults. BMI was classified as underweight ( < 18.5 kg/m2), normal weight (18.5-24.9), overweight (25.0-29.9), obese class I (30.0-34.9), and obese class II (≥35.0). We used Cox proportional hazards to examine the association between maximum lifetime BMI and BMI at survey and all-cause and specific causes of death (ie, cardiovascular disease, cancer, diabetes, and other) controlling for age, sex, and smoking in 6,242 Mexican American adults enrolled in NHANES III (1988-1994) and NHANES 1999-2010. Results Mexican Americans categorized as obese class II at maximum lifetime and time of survey had increased risk of all-cause mortality (hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.54 - 2.93 and HR, 1.52; 95% CI, 1.10-2.10). Those reporting a maximum lifetime BMI of class I or class II obesity but who were classified as normal weight at survey had increased risk of all-cause mortality (HR = 2.49; 95% CI, 1.72-3.61 and HR = 3.56; 95% CI, 1.15-11.06, respectively). Conclusion Increased all-cause mortality risk in Mexican Americans with a lifetime BMI of 35 or greater refutes prior studies, suggesting that maximum lifetime BMI should be included when evaluating obesity-mortality associations in this population.