Background: It is essential to understand the factors that affect the academic achievement of schoolchildren, both in general and in terms of the major subsectors of each grade. Although symptoms of Attention Deficit Hyperactivity Disorder (ADHD) and Negative Defiant Disorder (NDD—which are commonly recognized as externalizing problems in childhood and adolescence—have been associated with lower academic achievement in the international literature, few studies have addressed this problem in Latin America. This study aimed to analyze the possible predictive relationship of attention problems, hyperactivity, and defiant behavior on academic achievement. Methods: We recruited a sample of 4580 schoolchildren (50.9% female, 1754 belonging to primary school, and 2826 to secondary school, ranging from 9 to 18 years old). This cross-sectional study used the scales pertaining to attention problems, hyperactivity, and challenging behavior from the Child and Adolescent Evaluation System. Results: The analysis showed that attention problems significantly affected all academic achievement areas, while hyperactivity and challenging behavior affected only some of them. The regression models explained 24% of the variability in overall academic achievement in primary school and 17% in secondary school. Other predictors included sex, age, socioeconomic level, and school attendance. Conclusions: It is important to consider this symptomatology in the design of educational interventions.