This study compared the effect of two face-to-face(F2F) and e-learning education methods on learning, retention, and interest in English language courses. Participants were EFL students studying at Islamic Azad University, for the academic year 2021–2022. A multiple-stage cluster-sampling method was used to select the target participants. Three hundred and twenty EFL learners participated in the study. Students were studying in different majors: accounting, economics, psychology, physical education, law, management, and sociology. Two English tests were applied, a teacher-made VTS (Vocabulary Size Test) and an achievement test (including reading comprehension and grammar questions). Also, a questionnaire was applied to measure the students’ learning interest in F2F and online learning groups. The study found significant differences in learning outcomes related to students’ English learning and vocabulary retention rates. It was seen that the E-learning group that participated in online sessions through the Learning Management Systems (LMS) platform outperformed the F2F group. Another critical finding revealed that learners’ interest in learning English in E-learning classes was higher than in the F2F group. In addition, all constructs of interest (feeling happy, attention, interest, and participation) were higher in scores in the E-learning than in the F2F group. Language teachers, university instructors, educators, syllabus designers, school administrators, and policymakers might rethink their teaching approaches and incorporate E-learning into the curriculum to meet their students’ needs.