We examined depression and anxiety symptom trajectories in Mexican-origin youth (N = 674) and tested longitudinal associations with acculturation dimensions. We used eight waves of data from the California Families Project, collected annually from 5th (Mage = 10.86, SD = 0.51) to 12th (Mage = 16.79, SD = 0.50) grade. Major depression disorder (MD) and generalized anxiety disorder (GAD) symptoms were assessed by structured psychiatric interview. Cultural measures, selected based on theory and empirical evidence, included English/Spanish use, familism, traditional gender role (TGR) attitudes, and ethnic pride. Symptom trajectories were modeled using latent growth analyses, and parallel process growth models examined covariation between internalizing and acculturation trajectories. Models adjusted for child sex, nativity, mother's education, and family income. MD symptoms decreased across adolescence on average, with steeper decreases among boys and children born in Mexico. GAD symptoms also decreased on average, with higher mean levels among girls. Age 10 Spanish use, familism, and ethnic pride were inversely related to age 10 MD symptoms. Steeper increases in Spanish use, familism, and ethnic pride predicted decreasing MD. Higher age 10 MD predicted increasing Spanish use and decreasing English use. Greater age 10 TGR attitudes predicted higher age 10 GAD but steeper declines in GAD and MD. Increasing ethnic pride slopes predicted decreasing GAD. Greater childhood TGR attitudes, and the maintenance of Spanish use, familism, and ethnic pride into adolescence, were associated with more optimal trajectories of MD and GAD symptoms. Interventions for Mexican-origin youth internalizing problems should encourage the retention of heritage culture strengths, including familism and ethnic pride.