The current study set out to investigate the effect of strategy-based instruction (SBI) on motivation, self-regulated learning, and reading comprehension ability of Iranian English as a Foreign Language (EFL) learners. To fulfil the purposes of this study, 55 intermediate EFL learners were selected and randomly assigned to two groups including a control and an experimental one. Subsequently, the motivation and self-regulated learning questionnaires and a reading comprehension test were administered to the two groups as pretests. Then both groups underwent the same amount of teaching time (12 sessions) using the Developing Skills as a course book. The students in the experimental group also received the instruction of six reading strategies consisting of making connections, predicting, questioning, monitoring, visualizing, and summarizing. Finally, the two questionnaires and the reading comprehension test were administered as the posttests to both groups and the scores were compared using MANCOVA. The results of data analyses revealed that SBI significantly affected reading comprehension, motivation, and self-regulation (SR) of foreign language learners. Teachers are encouraged to employ SBI to enhance learners’ reading comprehension, motivation, and SR.