Background Reading comprehension is an essential skill not only during learning but also to successfully navigate everyday life. However, reading comprehension is a task that is challenging even among some adept readers. Thus, in the present investigation, we explored how to improve reading comprehension skills among a sample of middle school students (N = 124) in rural southeast Georgia, United States. Methods Employing a quasi‐experimental pre‐test/post‐test design, we randomly assigned six classrooms to serve as either intervention (three classrooms with n = 66 students) or control (three classrooms with n = 58 students). The treatment involved implementing evidence‐based literacy instruction across content areas by the three content‐area teachers whose classrooms formed part of the intervention group. Data on students' reading comprehension skill as measured by the Reading Inventory (RI) and Georgia Milestones Assessment System (GMAS) Lexile were collected at baseline (2018) and post‐test (2019). Results Results revealed that students exposed to literacy instruction across content significantly outperformed students in the control group on both post‐test RI and GMAS scores, after controlling for prior knowledge pre‐test scores, albeit the effect was three times larger for GMAS Lexile than RI scores. Conclusion Implementing literacy instruction across content areas is an effective method for enhancing reading comprehension. We discuss implications for research and practice considering these findings.