Abstract: With a framework of inquiry-based science teaching and learning, Web-based learning environment has been considered important. Related research persistently tried to identify the core variables that enhance the learning outcome of it. This study, hence, chose four possible variables: Self-Regulated Learning (SRL) skills, cognitive presence, science process skills, and science learning achievement scores and examined their structural relationship using Structural Equation Model analysis. The results show that SRL skills have a direct effect on cognitive presence and an indirect effect on science process skills and achievement scores with mediation of cognitive presence. Cognitive presence has a direct impact on science process skills and achievement scores and science process skills have a direct impact on achievement scores. Therefore, facilitation of students’ SRL skills may be able to stimulate students’ cognitive presence. This could be a critical success factor in such classes.