Nowadays, Calculus has got tremendous applications in Physics, Chemistry, Economics, Accounting and Engineering. However, learning Calculus concepts in high schools and higher institutions is found to be a challenging problem. Students have low motivation, poor conceptual understanding and reasoning in learning calculus concepts such as limit, continuity, derivative and definite integrals. Because of this, the overarching aim of the present study was to investigate students’ conceptual understanding, reasoning and motivation by applying GeoGebra software in multi-teaching approaches coupled with a genetic decomposition model grounded in APOS (Action, Process, Object & Schema) theory. The study involved an intervention mixed research design encompassing both the quantitative and qualitative approaches. A quasi- experimental design was employed for the quantitative approach and case study design was used for the qualitative method. Two universities were randomly selected out of Amhara Regional state universities. A pretest was administered to collect baseline information regarding the concept of calculus. Thereafter, first year physics students at U1 University were assigned as experimental group and first year physics students at U2 University were assigned as the comparison group using random sampling technique. Next, Calculus concepts were delivered using GeoGebra integrated with multi-teaching approaches coupled with a genetic decomposition model grounded in APOS theory, whereas the comparison group learned the same content using the traditional method for twelve weeks. Diagnostic Tests (Pretest, Mid-term Test & Posttest) and Motivation scales based on the ARCS (attention, relevance, confidence and satisfaction) model were employed to collect quantitative data, and semi structured questions and open-ended questions were used to collect qualitative data using students’ interview and reflections respectively. Descriptive Statistics, t-test, ANCOVA, Correlations and Multiple Regression were employed to analyze the quantitative data. However, thematic analysis and descriptive analysis were used for analyzing the qualitative data. The results from the analyses of quantitative data revealed that the treatment group got significantly higher mean scores on conceptual understanding, reasoning and motivation than the comparison group. Hence, the findings emerged out of this study indicated that the implementation of GeoGebra software together with multi-teaching approaches coupled with genetic decomposition model grounded in APOS theory improves students’ calculus learning better than the traditional approach. On the other hand, results from the qualitative data uncovered that GeoGebra integrated with multi-teaching approaches improves students’ interest, vi motivation, visualization and understanding of calculus concepts. Moreover, students elicited manifestation of constructions of mental structures in a coherent and logical manner while learning calculus activities designed based on a genetic decomposition model grounded in APOS theory. In sum, the finding showed that GeoGebra integrated with multi-teaching approaches guided with APOS theory is effective to enhance students’ motivation, conceptual understanding and reasoning in learning calculus concepts. The finding opens a greater opportunity to recommend technology integrated mathematics curriculum in Ethiopian higher education. Key Words: GeoGebra Software, Multi-teaching, Conceptual Understanding, APOS theory, Motivation