This article follows the early-stage planning, implementation, and evaluation of a university–school-based partnership (USBP) between a large Carnegie-designated doctoral research institution (R2) and local high schools in Georgia. The purpose of the partnership was to implement suicide and substance use prevention efforts over 3 years. USBPs are mutually beneficial to partners and provide opportunities for positive change within the larger community. Two evidence-based prevention programs were implemented: Sources of Strength (SOS) and Mindfulness-Based Stress Reduction (MBSR). The authors describe the development and evolution of the partnership as well as the prevention programs with underserved student populations, lessons learned over the 3 years, and early-stage positive implications for sustaining the project.