We analyzed two nationally representative, longitudinal data sets of U.S. children to identify risk factors for persistent mathematics difficulties (PMD). Results indicated that children from low socioeconomic households are at elevated risk of PMD at 48 and 60 months of age, as are children with cognitive delays, identified developmental delays or disabilities, and vocabulary difficulties. In contrast, children attending preschool either in Head Start or non-Head Start classrooms are at initially lower risk of PMD. Kindergarten-aged children experiencing either low socioeconomic status or mathematics difficulties are at greatest risk for PMD across third, fifth, and eighth grades. Also at risk for PMD between third and eighth grades are children displaying reading difficulties or inattention and other learning-related behaviors problems, children with identified disabilities, and those who are retained. Educationally relevant and potentially malleable factors for decreasing young children's risk for PMD may include increasing children's access to preschool, decreasing their risk of experiencing vocabulary or reading difficulties, and avoiding use of grade retention.