Enamel formation is a vulnerable developmental process, susceptible to environmental influences such as excessive systemic fluoride (F) exposure and infant/childhood disease. This study determined prevalence and extent of developmental enamel defects (DDE) and dental fluorosis in 8-year-old Nigerians and explored associations with key predictors. A sample of 322 healthy 8-year-olds (155 males, 167 females) from primary schools in lower and higher water F areas of (i) rural and (ii) urban parts of Oyo State in south-west Nigeria (n = 4 areas) (in which the mean (SD) F concentration of community water supplies ranged from 0.07 (0.02) to 2.13 (0.64) mg F/L) were dentally examined using modified DDE (mDDE) and Thylstrup and Fejerskov (TF) indices. Drinking waters, cooking waters and toothpaste samples were analysed for F concentration using a F ion-selective electrode (F-ISE). Information on infant/childhood diseases, infant feeding and tooth cleaning practices was obtained from parents/legal guardians. Data were analysed using ANOVA, chi-square tests, Spearman correlation and binary logistic regression as appropriate. Mean (SD) F concentration of actual drinking and actual cooking waters consumed by participants was 0.25 (0.20) and 0.24 (0.14) mg F/L respectively in the urban higher F area; 1.11 (1.00) and 1.16 (1.02) mg F/L, respectively in the rural higher F area (P < .05). Overall, mouth prevalence of DDE in the permanent dentition was 61.2% with a mean (SD) of 2.4 (2.2) index teeth affected. Dental fluorosis mouth prevalence was 29.8% with a mean of 2.1 (3.7) teeth affected. Prevalence and extent of DDE and dental fluorosis were greater in higher F than lower water F areas (P < .001). A weak positive correlation was seen between extent of dental fluorosis and drinking water F concentration (ρ = 0.28). The absence of infant/childhood disease was associated with a lower risk of DDE being present (P = .001), with an odds ratio of 0.43 (95% CI = 0.26, 0.71). Gender was a statistically significant (P = .014) predictor for dental fluorosis with females having a higher risk OR 1.94 (95% CI = 1.14, 3.28) of dental fluorosis than males. In these Nigerian 8-year-olds (n = 322), mouth prevalence of DDE was 61.2% (mean (SD) teeth affected = 2.4 (2.2)), and a key positive predictor was a history of infant/childhood disease. With 29.8% of these children exhibiting dental fluorosis (mean (SD) teeth affected = 2.1(3.7)), drinking water F concentration was identified as a positive predictor, along with gender, with females more at risk of dental fluorosis than males.