A new learning unit in chemistry, "Case-based Computerized Laboratories" (CCL) and Computerized Molecular Modeling" (CMM) was developed at the Technion. The CCL and CMM curriculum integrates computerized desktop experiments and molecular modeling with an emphasis on scientific inquiry and case studies. Our research aimed at investigating the effect of the CCL and CMM learning environment on students' higher-order thinking skills of question posing, inquiry, and modeling. The experimental group included 614 honors 12th grade chemistry students from high schools in Israel who studied according to this learning unit. The comparison group consisted of 155 12th grade chemistry honors students who studied other chemistry programs. Pre- and post-tests questionnaires were used to assess students' higher-order thinking skills. Students' responses were analyzed using content analysis rubrics and their statistical analysis. Our findings indicated that the scores of the experimental group students improved significantly in question posing, inquiry and modeling skills from the pre-test to the post-test. The net gain scores of the experimental group students were significantly higher than those of their comparison peers in all three examined skills. In modeling skills, experimental group students significantly improved their achievements in making the transfer from 3D models to structural formulae, but only about half of them were able to transfer from formulae to 3D models. By presenting a case-based chemistry assessment tool and content analysis of students' responses in this paper, we enable teachers and educators to analyze their students' higher-order thinking skills both qualitatively and quantitatively.