Many studies have examined the effect of argumentation-based instruction methods on student achievement in the literature. However, there was no mixed-research synthesis study providing a holistic overview of quantitative and qualitative research findings of primary studies. To fill this gap in the literature, the study investigated the effects of argumentation-based instructional practices on student achievement. It also aimed to reveal the factors affecting these practices by combining the quantitative and qualitative research findings. Therefore, a mixed-research synthesis was employed to achieve this purpose. The study included 72 quantitative and 22 qualitative studies. The data obtained from the quantitative studies were combined using a meta-analysis method, and the qualitative data were combined using a thematic synthesis method. Several analytical themes were created regarding the factors affecting argumentation-based instruction, and various analytic themes (recommendations/hypotheses) were developed accordingly. According to the data from the thematic synthesis, 13 analytical themes emerged. The meta-analytic results indicated that the argumentation method had a large positive effect on student achievement (g = 0.927, 95% CI [0.789, 1.064]). Also, the moderator analysis revealed that argumentation-based instruction highly affected student achievement in Chemistry and Mathematics than others. Also, the time allocated to courses was influential in increasing student achievement. Lastly, attempts were made to explain the variance between studies included in the meta-analysis using the analytical themes developed in the thematic synthesis. The thematic synthesis results indicated that the learning outcomes and the environment should be taken into consideration in argumentation-based instruction and that some deficiencies should be resolved.