Purpose: Research indicates that a culture of learning is a key factor in building high schools that foster academic achievement in all students. Yet less is known about which elements of a culture of learning differentiate schools with higher levels of academic performance. To fill this gap, this comparative case study examined the cultures of learning among adults and students in two highly effective high schools and two less effective high schools with similar demographics in a single large, urban school district. Research Method: Using 135 interviews and focus groups with administrators, teachers, and students across four case study schools, the authors analyzed the extent to which various elements of a culture of learning was present within and across schools. Findings: Effective high schools had stronger cultures of learning with distinct structures and practices that distinguished them from the less effective schools. These included frequent opportunities for formal collaboration, shared goals centered on universal high expectations, structured opportunities for participatory leadership, and deliberate supports to help students engage and achieve in academics. Findings further revealed that certain structures were necessary though not sufficient in fostering effective cultures of learning, the active role of school leaders in reinforcing a culture of learning, and high leverage practices that addressed multiple elements of a culture of learning. Implications: This study provides implications for how school leaders can begin to create and improve on school-wide cultures of learning by drawing on the high leverage practices that distinguished the highly effective case study schools.