The purpose of this formative evaluation was to examine the impact of an innovative inquiry based science education curriculum for middle school students, called Choice, Control, and Change, that is designed to foster healthful eating and physical activity and a healthy weight through enhancing agency and competence. The 24-session curriculum helps students develop understandings about the interactions between biology, personal behavior, and the environment and personal agency through cognitive self-regulation skills in navigating today’s complex food system and sedentary environment. An extended theory of planned behavior served as the design framework. The study used a pretest-posttest evaluation design involving 278 middle school students in 19 science classes within 5 schools. Based on paired t tests, students significantly improved on several curriculum-specific eating and physical activity behaviors: they decreased several sedentary activities and increased their frequencies of fruit and vegetable intake. They decreased the frequency of sweetened beverages, packaged snacks, and eating at a fast-food restaurant, and ate and drank smaller portions of some items. Their outcome beliefs and overall self-efficacy, but not their attitudes, became more positive. A strategy based on fostering personal agency, cognitive self-regulation, and competence can be effective in increasing healthful eating and physical activity behaviors in middle school children and should be explored further.