This study investigated the efficacy of a multi-component reading comprehension instructional approach, Collaborative Strategic Reading (CSR), compared to business-as-usual instructional methods with 19 teachers and 1074 students in middle school social studies and science classrooms in a large urban district. Researchers collaborated with school personnel to provide teachers with ongoing professional development and classroom support. Using an experimental design, teachers' classrooms were assigned either to CSR or to a business-as-usual comparison condition. Multi-level analyses showed that students receiving CSR instruction scored higher on a standardized reading comprehension assessment compared to their peers in comparison classrooms (g = 0.18, p < 0.05). While implementation varied across classrooms, students in the CSR condition were observed using CSR strategies and working together in small groups. Teachers attended to the quality of student work and provided more feedback when teaching CSR. CSR is an effective method to improve the reading comprehension of adolescents and to increase their access to complex informational text.