The use of guided inquiry-based learning (GIBL) in a manner designed to challenge individual students’ unscientific conceptions of science, has been researched widely. However, few (if any) studies have investigated the implementation of GIBL in a manner designed to challenge the fundamental patterns of students’ context-dependent unscientific conceptions of science. This study investigates the effect of GIBL on transforming the fundamental patterns of Ethiopian eighth-grade students’ context-dependent conceptions, schemes of knowledge, about vision. The study used a quasi-experimental pre–post design with a mixed method approach. We measured conceptual change using qualitative and quantitative assessments based on facet-scheme frequencies. Treatment-group students’ conceptions expressed in a facet-scheme structure were compared with those of students receiving conventional instruction (CI). Before instruction, both student groups subscribed to spontaneous (observer not connected with the object/image) and inclusive (observer incorrectly connected with the object/image) vision schemes. After instruction, the frequencies of these schemes were decreased to a greater extent among GIBL students than CI students. The scientific scheme was observed with more frequency among GIBL students than CI students. We therefore conclude that GIBL transformed the students’ schemes of knowledge from unscientific to scientific to a greater extent than CI. The study points out vital practical implications for educators.