The purpose of this study was to document the design, classroom implementation, and effectiveness of interactive online units to enhance science learning over 3 years among students with learning disabilities, English learners, and general education students. Results of a randomised controlled trial with 2,303 middle school students and 71 teachers across 13 schools in two states indicated that online units effectively deepened science knowledge across all three student groups. Comparing all treatment and control students on pretest-to-posttest improvement on standards-based content-specific assessments, there were statistically significant mean differences (17% improvement treatment vs. 6% control; p < 0.001); no significant interactions were found between treatment condition and learning disability or English learner status, indicating that these two groups performed similarly to their peers; students with learning disabilities had significantly lower assessment scores overall. Teachers and students were moderately satisfied with the units.