Childhood temperament and family environment characteristics have been shown to predict children’s internalizing and externalizing behavior; however, less is known about how temperament and family environment interact to predict changes in problem behavior. We conducted latent growth curve modeling on a sample assessed at ages 5, 7, 10, 14, and 17 (N = 337). Externalizing behavior decreased over time for both sexes, and internalizing behavior increased over time for girls only. Two childhood variables (fear/shyness and maternal depression) predicted boys’ and girls’ age-17 internalizing behavior, harsh discipline uniquely predicted boys’ age-17 internalizing behavior, and maternal depression and lower family income uniquely predicted increases in girls’ internalizing behavior. For externalizing behavior, an array of temperament, family environment, and Temperament x Family Environment variables predicted age-17 behavior for both sexes. Sex differences were present in the prediction of externalizing slopes, with maternal depression predicting increases in boys’ externalizing behavior only when impulsivity was low, and harsh discipline predicting girls’ externalizing behavior only when impulsivity was high or when fear/shyness was low.