Background: Inadequate volumes of physical activity may be associated with the increases in inappropriately high weight in children of 5 years of age and younger. Preschools have typically lacked sufficient time in daily physical activity. Purpose: A preschool-administered physical activity treatment based on social cognitive and self-efficacy theory (Start For Life) was tested for its association with increased physical activity and reduced body mass index (BMI). Methods: Data from accelerometer and BMI assessments over a 9-month preschool year (18 treatment and 8 control classes of 17 to 20 children each; mean age = 4.4 years) were used to contrast the behaviorally based treatment of 30 min per day with a usual care condition of the same duration. The sample was primarily African-American. Preschool teachers administered all processes. Results: The Start For Life treatment was associated with a significantly greater percentage of the preschool day in moderate-to-vigorous and vigorous physical activity (approximately 30 min per week more), with sedentary time unaffected. The treatment was also associated with a significant reduction in BMI, with effect sizes greatest in overweight and obese children. Conclusions: Although results were positive in contrast to usual care and other related interventions, the specific sample requires that the Start For Life treatment undergo sufficient replication to increase confidence in generalizability of the findings to others. Although reduction in sedentary time may require a different strategy, the practical application of the present treatment suggests possibilities for addressing overweight through increasing moderate-to-vigorous physical activity in preschool settings. © 2013 International Society of Behavioral Medicine.