There have been many practical obstacles for teachers to implement evidence-based educational technology, especially in STEM classrooms. By implementing learning principles related to Cognitive Load Theory, we developed an innovative Technology-Assisted Guided Learning (TAGL) approach and its web-based instructional tool, combining expertise from educational research and best teaching practices to enhance guided student-centered learning in chemistry. A total of 185 community college students were randomly assigned to learn stoichiometry through either TAGL or one of two active control interventions, traditional direct instruction and Khan Academy, a widely used web learning platform. We found that the TAGL group significantly outperformed both active control groups immediately after instruction, and furthermore, despite the fact that all groups received additional instruction in stoichiometry, the beneficial effects of TAGL compared to the control groups were maintained a month later. Notably, TAGL was able to eliminate the achievement gap between students with low prior knowledge and students with high prior knowledge. Furthermore, prior-knowledge activation was found to be especially beneficial for students with low prior knowledge. Our work contributes to existing research in learning theories and provides new insight toward the development of more effective and adaptive instructional designs. By translating research into practice, this study demonstrates the great potential of using innovative computer-based technology to improve student learning for all.