As funding for large translational research consortia increases across the National Institutes of Health (NIH), focused working groups provide an opportunity to leverage the power of unique networks to conduct high-impact science and offer a strategy for building collaborative infrastructure to sustain networks long-term. This sustainment leverages the existing NIH investments, amplifying the impact and creating conditions for future innovative translational research. However, few resources exist that detail practical strategies for establishing and sustaining working groups in consortia. Here, we describe how the Coordinating Center for the National Cancer Institute-funded Cancer Center Cessation Initiative (C3I) utilized principles derived from the Science of Team Science to develop replicable strategies for building and sustaining an effective working group-led consortium. These strategies include continually engaging community members in strategic planning, prioritizing diversity in leadership and membership, creating multi-level opportunities for leadership and participation, providing intensive community management and facilitation, and incentivizing projects that support the consortium sustainment. When assessing the impact of these interventions through qualitative exit interviews, four key themes emerged: through the C3I working group consortium, members co-created new dissemination products, gained new insights and innovations, enhanced local program implementation, and invested in cross-network collaboration to support sustained engagement in the initiative.