The Healthy Children Arizona (HCA) program was developed to promote early, positive exposure to cancer-preventive diet, physical activity and sun safety behaviors. Five lessons delivered weekly were evaluated by classroom teachers while pre- and post-curriculum surveys examined increases in students’ understanding of concepts and self-reported behavior. The first and second graders and their teachers in ethnically diverse elementary schools (including Title 1) in Tucson and Phoenix, Arizona participated in the curriculum assessment. All 5 interactive lessons were highly rated by teachers in qualitative assessments. Aggregated analyses of pre- (n = 582) and post- (n = 588) comparison tests indicated that the HCA curriculum significantly increased students’ knowledge of each of six measured concepts (p < 0.0001), although correct choice of muscle-building foods (25%), whole grain items (78%) and target time for daily exercise (61%) were lower than desired. Mean self-reported fruit and vegetable servings eaten in the previous day increased from 3.1 ± 1.8 to 3.8 ± 1.6 (p < 0.0001). The HCA curriculum significantly improved cancer prevention knowledge among primary school children.