The Midwest Expansion of the Child-Parent Center Education Program (MCPC) is a pre-K to 3rd grade intervention program aimed at improving economically disadvantaged children’s school success by enhancing continuity in instruction and increasing parental involvement. Opened in Chicago in the 1960s, this school reform model has undergone significant changes and is currently being expanded in five demographically heterogeneous school districts in Illinois and Minnesota. This article describes the collaborative process that has contributed to effective implementation of the expansion project within at-risk communities. Three themes of collaboration are emphasized: (a) improving the quality of data, (b) establishing and maintaining implementation fidelity, and (c) using research to inform practice. We discuss lessons learned from our partnerships with a number of collaborators including those involved with implementing the pre-K program, researching and evaluating the project, and providing professional development to teachers. Consideration is given to advancing the field of implementation science by successfully initiating and enhancing exemplary partnerships in comprehensive school reforms through effective research design.