Although there are a number of research-validated substance use prevention programs available for wide-scale dissemination, very little is known about the factors that influence adoption of evidence-based prevention programs in schools. We tested a model of the mechanisms of program adoption in schools that was guided by diffusion of innovations and social ecological theories. Cross-sectional data were collected from a sample of school district and county office of education tobacco use prevention education coordinators throughout California. Structural equation modeling was used to test the effects of community and organizational variables on the adoption of prevention programs via school administrators' beliefs and the organization's receipt of funding for the program. Results supported the hypothesis that the process of adoption begins with forming beliefs about the program, leading to adoption through the receipt of funding. In addition, we found direct effects of various community- and organizational-level factors on beliefs, receipt of funding, and adoption. These results are likely to inform policies that affect school districts' use of evidence-based substance use prevention programming, which should ultimately lead to reductions in negative health outcomes among adolescents. Specifically, this study identifies various factors that could be targeted for improvement to enhance evidence-based program adoption. To our knowledge, this is the first study to empirically elucidate the process of adoption of evidence-based tobacco prevention programs in schools.