Obesity prevention in children offers a unique window of opportunity to establish healthful eating and physical activity behaviors to maintain a healthful body weight and avoid the adverse proximal and distal long-term health consequences of obesity. Given that obesity is the result of a complex interaction between biological, behavioral, family-based, and community environmental factors, intervention at multiple levels and across multiple settings is critical for both short- and long-term effectiveness. The Minnesota NET-Works (Now Everybody Together for Amazing and Healthful Kids) study is one of four obesity prevention and/or treatment trials that are part of the Childhood Obesity Prevention and Treatment (COPTR) Consortium. The goal of the NET-Works study is to evaluate an intervention that integrates home, community, primary care and neighborhood strategies to promote healthful eating, activity patterns, and body weight among low income, racially/ethnically diverse preschool-age children. Critical to the success of this intervention is the creation of linkages among the settings to support parents in making home environment and parenting behavior changes to foster healthful child growth. Five hundred racially/ethnically diverse, two-four year old children and their parent or primary caregiver will be randomized to the multi-component intervention or to a usual care comparison group for a three-year period. This paper describes the study design, measurement and intervention protocols, and statistical analysis plan for the NET-Works trial.