Children’s early development is influenced by characteristics of the child, family, and environment, including exposure to substance abuse. The aim was to examine the association of early childhood development (ECD) with the prevalence of psychoactive substance use in Mexican municipalities. We obtained ECD data from the 2015 Survey of Boys, Girls, and Women (ENIM, for its Spanish acronym), measured with the ECD Index. The prevalence of psychoactive substance use was estimated at the municipal level, using the 2016 National Survey of Drug, Alcohol, and Tobacco Use (ENCODAT, for its Spanish acronym). Multilevel logistic models were fitted to evaluate the association between drug use and inadequacies in ECD overall and in four specific ECD domains: socio-emotional, literacy-numeric, learning, and physical. Inadequate ECD was directly associated with illegal drug use (OR = 1.10; 95% CI: 1.03, 1.17). For the specific ECD domains, inadequate socio-emotional development was directly associated with illegal drug use (OR = 1.08; 95% CI: 1.01, 1.15). These findings suggest that exposure to illegal drug use may influence ECD, and especially can lead to socio-emotional problems, although this cannot be considered the unanimous determinant of the problems presented. The implementation of evidence-based interventions to prevent drug abuse is necessary.