English language skills are considered of great value in the labor market and in the field of research. As such, learning English as a Foreign Language (EFL) becomes of great importance, especially for foreign students and employees working in international settings. The goal of the present study was to explore students’ self-efficacy in language learning (LSE), in contrast with general self-efficacy (GSE) and effort (EF) as predictors of students’ reading comprehension performance in English. Moreover, we hypothesized that effort mediates the relationship between LSE and reading comprehension performance. We explored the EFL learners who enrolled in academic English courses during a period of three months, one academic semester. Using a longitudinal design, at Time 1, the sample of 265 participants completed three questionnaires: GSE, LSE and EF scales. At Time 2, reading comprehension test was given to the participants who had completed the questionnaires previously. Results indicated that LSE, in contrast with GSE, is positively correlated with reading comprehension performance. Furthermore, the data showed that LSE is positively correlated with effort, and that effort is positively correlated with reading comprehension performance. Findings revealed that effort mediates the relationship between LSE and reading comprehension performance. Thus, our study contributes to the development of more effective teaching methods and provides EFL teachers the necessary tools to predict and enhance students’ achievements in the field. Implications and limitations for future research are discussed.