This study aims to develop multi-representation model e-worksheets to improve students' systems thinking skills on the human locomotor system. This study is a research and development (R & D) that refers to the 10 steps of Gall et al.'s model development. This study involved 100 students and 11 teachers at the information gathering stage, 2 e-worksheets validators at the limited field test stage, the main field test involved 15 students and 2 science teachers, while the operational field trial involved 64 students in grades VII.2 and VII.3 at SMP Negeri 2 Sekampung using a pretest-posttest control group design. The instruments in this study included a questionnaire on teacher and student needs, a questionnaire on e-worksheet validation aspects of content, construction and readability, a questionnaire on student and educator responses to e-worksheets, and pretest-posttest questions on systems thinking skills. The qualitative data analysis technique in this study used descriptive analysis and quantitative data used an independent sample t-test. The results of the validation of e-worksheets by experts stated that the developed e-worksheets were valid with the criteria of “very high” and based on the responses of teachers and students, the practical e-worksheets had the criteria of “very high”. The results of the independent sample t-test obtained a sig.2 tailed value of 0.000, meaning that the average value of the systems thinking skills of students in the experimental class was higher than the control class, with an average n-gain in the control class of “0.32” while the experimental class was “0.71”. This is supported by the results of the effect size test of “0.871” which states that the developed e-worksheets have a very large influence in improving students' systems thinking skills