Background: Multiple interventions have been tested to promote well-being in high school students, often focusing on depression prevention. Aims: To test the impact of a one-semester active learning curriculum covering the modern science and philosophy of well-being and happiness on attitudinal measures related to the curriculum and standard measures of depression and well-being. Sample: Subjects were first-year students in an urban high school in Beijing, China (equivalent to US tenth grade). Methods: Nine classrooms were randomly assigned to the intervention curriculum (n = 252), and nine classrooms were randomly assigned to a traditional psychology curriculum (n = 263). Students completed questionnaires pre- and post-semester including a Positive Attitude Scale (PAS, concerning Relatedness, Competence, Autonomy, Gratitude, Calmness, Mindfulness, and Hope), Positive and Negative Affect Scale (PANAS), Centers for Epidemiological Studies Depression Scale (CES-D), Life Satisfaction Scale (LS), Subjective Happiness Scale (SHS), Meaning in Life Questionnaire (MLQ), and a test of knowledge about well-being (Knowledge Test, KT). Results: In a hierarchical linear model, there were statistically significant intervention effects on six of the seven subscales of the PAS, on PANAS balance, and on the KT. CES-D, LS, SHS, and MLQ were improved but not significantly so. Notable overall secular trends in measures of well-being were observed, with a peak in September and nadir in April. Conclusions: A one-semester course for high school students regarding well-being and happiness demonstrated significant changes in positive attitudes, affective balance, and knowledge about happiness. Circannual trends in well-being measures over the academic year have implications for those designing school intervention studies.