Supporting the reading comprehension and content knowledge acquisition of English language learners (ELs) requires instructional practices that continue beyond developing the foundational skills of reading. In particular, the challenges ELs face highlight the importance of teaching reading comprehension practices in the middle grades through content acquisition. We conducted a randomized control trial to examine the efficacy of a content acquisition and reading comprehension intervention implemented in eighth-grade social studies classrooms with English language learners. Using a within-teacher design, in which 18 eighth-grade teachers' social studies classes were randomly assigned to treatment or comparison conditions. Teachers taught the same instructional content to treatment and comparison classes, but the treatment classes used instructional practices that included comprehension canopy, essential words, knowledge acquisition, and team-based learning. Students in the treatment group (n = 845) outperformed students in the comparison group (n = 784) on measures of content knowledge acquisition and content reading comprehension but not general reading comprehension. Both ELs and non-ELs who received the treatment outperformed those assigned to the BAU comparison condition on measures of content knowledge acquisition (ES = 0.40) and content-related reading comprehension (ES = 0.20). In addition, the proportion of English language learners in classes moderated outcomes for content knowledge acquisition.