This study examined the effects of a content area reading instruction (treatment) implemented by middle school social studies teachers. Two teacher participants were recruited from one public school in Taipei. Overall, 182 students from teacher participants’ classes were recruited for treatment condition, and another 119 student participants were recruited for comparison from another public school. There were a total of 301 participants, all of which were seventh- and eighth-graders. Using a quasi-experimental design, baseline equivalence between treatment and comparison groups was established on the related reading measures. The treatment instruction was a Tier-1, six-session content area reading instruction focusing on ocean topics in social studies. All the treatment lessons, including detailed instructional scripts, texts, and teaching materials, were developed and provided to the teachers by the researcher. The comparison group was not exposed to any reading instructions, nor to the texts and materials of the treatment instruction. A treatment fidelity check including adherence and quality of delivery was conducted during the entire teaching by observations to ensure the treatment fidelity. The overall treatment effect on students was examined on the entire sample. Next, 38 and 31 students with reading difficulties were identified according to the general reading comprehension measure in both groups. The treatment effects on students with reading difficulties were further examined using this subsample. Results showed that students who received the treatment outperformed those in the comparison group on proximal measures, including academic vocabulary, content area knowledge, and content area reading comprehension. The content-area reading comprehension performance of students with reading difficulties remained consistent with treatment but significantly decreased in comparison. In addition, the results indicate that the treatment was facilitative for students both with and without reading difficulties in general classrooms, implying the effectiveness as well as the importance of the evidence-based content area reading instruction implemented in the Tier-1 setting. Further conclusions and suggestions concerning content area instructional practices were specified based on the findings of the study.