Evidence suggests that coronavirus disease 2019 (COVID-19) testing in schools can add a layer of protection to reduce the spread of Severe Acute Respiratory Syndrome Coronavirus 2 and facilitate a safer return to in-person learning. Despite this evidence, implementation of testing in school settings has been challenging initially because of a lack of funding and limited availability of testing, but, as the pandemic has progressed and more funding and resources have been devoted to testing, other implementation challenges have arisen. We describe key implementation barriers and strategies that have been operationalized across 5 projects working to help schools with predominantly underserved populations who have faced significant COVID-19–related health disparities. We leveraged a key framework from the implementation science field to identify the challenges and used a matching tool to align implementation strategies to these challenges. Our findings suggest that the biggest obstacles to COVID-19 testing were the perceived relative advantages versus burden of COVID-19 testing, limited engagement with the target beneficiaries (eg, families, students, staff), and innovation complexity. Common strategies to overcome these challenges included identifying and preparing testing champions, altering incentive and allowance structures, assessing for readiness, and identifying barriers and facilitators. We aim to augment existing implementation guidance for schools by describing common barriers and recommended solutions from the implementation science field. Our results indicate a clear need to provide implementation support to schools to facilitate COVID-19 testing as an added layered mitigation strategy.