The San Francisco Gartersnake (Thamnophis sirtalis tetrataenia), one of North America’s most endangered snakes, persists in fragmented habitat across San Mateo and northern Santa Cruz counties. To avert extinction, San Francisco Zoo & Gardens, in partnership with the U.S. Geological Survey, National Park Service, U.S. Fish & Wildlife Service, California Department of Fish and Wildlife, Golden Gate National Parks Conservancy, and Midpeninsula Regional Open Space District, has launched the first head-start program for this species. This collaborative conservation initiative builds on decades of work—from managing confiscated snakes in the 1990s to advancing research on genetics, fecundity, and population modeling that informed our approach. In 2025, the program achieved a major milestone with the collection of gravid females from the wild and the successful birth of neonates at the Zoo, marking the first head-started cohort for future reintroduction. We present the methodology behind our head-starting efforts, early outcomes from the inaugural cohort, and critical next steps needed to recover this iconic species. This project demonstrates how long-term partnerships, applied research, and zoo-based conservation programs can directly contribute to reversing population declines in one of California’s most imperiled reptiles.