This study investigates the impact of e-learning on students’ achievement in chemistry, guided by three research questions and one hypothesis. Using a quasi-experimental pretest-posttest design with a non-randomized control group, 21 Senior Secondary School Two (SS2) chemistry students from four coeducational schools in Nnewi North were randomly selected. Data collection involved a Chemistry Achievement Test (CAT) sourced from WAEC past questions, a Computer Assisted Instructional Package (CAIP), YouTube, and the Chemistry Performance Test (CHEMPET). Instrument reliability, verified through Cronbach alpha procedures, yielded a value of 0.83. Analysis of the data, employing mean, standard deviations, and a significance level of 0.05 in the t-test for the hypothesis, revealed that students using e-learning performed better on post-tests and knowledge retention exams. Notably, female students outperformed males in e-learning-supported teaching. The study underscores the significant difference in performance between male and female pupils exposed to e-learning. Recommendations emphasize the importance of supporting educational computer programs like e-learning for effective teaching and learning of chemistry, calling on curriculum designers, policymakers, and educators to integrate such practical approaches.