Objectives We investigated the relationship between early childhood malnutrition‐related measures and subsequent enamel defects in the permanent dentition. Materials and Methods This cohort study included 349 Amerindian adolescents (10–17 years, 52% male) from the Bolivian Amazon. Exposures included: stunted growth (height‐for‐age z‐scores), underweight (weight‐for‐age z‐scores), anemia (hemoglobin), acute inflammation (C‐reactive protein) and parasitic infection (hookworm). We measured the occurrence (no/yes) and extent (<1/3, 1/3–2/3, >2/3) of enamel defects. We estimated associations between childhood exposures and enamel defect measures using log‐binomial and multinomial logistic regression. Results The prevalence of an enamel defect characterized by an orange peel texture on a large central depression on the labial surface of the central maxillary incisors was 92.3%. During childhood (1–4 years), participants had a high prevalence of stunted growth (75.2%), anemia (56.9%), acute inflammation (39.1%), and hookworm infection (49.6%). We observed associations between childhood height‐for‐age (OR = 0.65; P = 0.028 for >2/3 extent vs. no EH) and gastrointestinal hookworm infection (OR = 3.43; P = 0.035 for >2/3 extent vs. no defects or <1/3 extent) with enamel defects. Discussion The study describes a possibly novel form of enamel hypoplasia and provides evidence for associations of malnutrition‐related measures in early childhood, including stunted growth and parasitic helminth infection, with the observed enamel defects.