Children with intellectual and developmental disabilities (IDD) and children with medical complexity (CMC) have been disproportionally impacted by the COVID-19 pandemic, including school closures. Children with IDD and CMC rely on schools for a vast array of educational, therapeutic, medical, and social needs. However, maintaining safe schools for children with IDD and CMC during the COVID-19 pandemic may be difficult due to the unique challenges of implementing prevention strategies, such as masking, social distancing, and hand hygiene in this high-risk environment. Furthermore, children with IDD and CMC are at a higher risk of infectious complications and mortality, underscoring the need for effective mitigation strategies. The goal of this report is to describe the implementation of several screening testing models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this high-risk population. By describing these models, we hope to identify generalizable and scalable approaches to facilitate safe school operations for children with IDD and CMC during the current and future pandemics.