Little is known about body size over the life-course and non-communicable disease risk in low- and middle-income country populations. Our study explored the role of body mass index (BMI) trajectories from infancy through mid-adulthood on cardio-metabolic disease (CMD) risk factors in a prospective cohort of Guatemalan adults. Study participants were born in Guatemala from 1962-77 and have been followed prospectively since participating in a nutrition supplementation trial as children. Sex-specific BMI latent class trajectories were derived using latent class growth modeling from up to 22 possible BMI values from age 1 month to 42 years measured between 1969 and 2004. CMD risk factors were assessed in 2015-17 (at age 37-54 years) using anthropometry, blood glucose and lipids, and blood pressure. We used logistic regression to assess the role of BMI trajectory on CMD risk factors in 510 women and 346 men (N = 856). We identified two BMI latent classes for women (low [n = 287, 56.3%] and high [n = 223, 43.7%]) and three classes for men (low [n = 141, 40.8%], medium [n = 160, 46.2%], and high [n = 45, 13.0%]). Given the small percentage of men in the high BMI latent class, we collapsed the medium and high BMI latent classes for men (n = 205, 59.1%). Among the most prevalent CMD risk factors at ages 37-54 years were abdominal obesity defined by waist-height ratio (99.6% of women and 87.3% of men), obesity defined by percent body fat (96.6% of women and 75.9% of men), low HDL-c (87.5% of women and 74.5% of men), and elevated triglycerides (78.3% of women and 73.6% of men). Except for obesity defined by BMI, we found no associations between BMI latent class and CMD risk factors in women. Among men, BMI latent class was not associated with CMD risk factors after controlling for current BMI. For the CMD risk factors we analyzed, the role of early life BMI on adult CMD appeared to be mediated by adult BMI among men-highlighting the need to establish and maintain healthy body weight over the life course.