Escalating evidence for the fetal impact of Zika virus infection required a change in care by all prenatal providers. This article describes an effective model of rapid implementation of universal prenatal screening at one hospital and its network of community health centers for a large and diverse immigrant population exploring the challenges, experiences, and lessons learned. Implementation of national recommendations required a workflow change, challenging a system with a heterogeneity of settings and providers. Using a physician clinical champion and advanced practice nurses in the roles of logistical coordinator and liaison to the network, Zika screening was embedded into prenatal intake visits at both the hospital and community health centers. Challenges addressed include varied medical record systems, acceptance by patients, providers, and community health center leadership, as well as culturally appropriate outreach to diverse ethnic and linguistic communities. In 6 months, the prenatal screening rates increased from 20% to 88%, which resulted in the identification of more than 300 pregnant patients at risk of exposure to Zika virus. This model offers key lessons for emergency preparedness in heterogeneous, safety net hospital settings.