Recent reforms in K-16 science education advocate for the integration of science content and practice. However, engaging students in authentic science practices can be particularly challenging for certain subjects such as evolution. We describe Avida-ED, a research-based platform for digital evolution that overcomes many of the challenges associated with using biological model organisms in the classroom. We then report the findings of a nationwide, multiple-case study on classroom implementation of Avida-ED and its influence on student understanding and acceptance of evolution. We found that engagement in lessons with Avida-ED both supported student learning of fundamental evolution concepts and was associated with an increase in student acceptance of evolution as evidence-based science. In addition, we found a significant, positive association between increased understanding and acceptance. We discuss the implications of supporting reform-based pedagogical practices with tools such as Avida-ED that integrate science content with authentic science practice.