The aim of this study is to investigate the effect of argument-driven inquiry (ADI) based laboratory instruction on the academic achievement, argumentativeness, science process skills, and argumentation levels of pre-service science teachers in the General Physics Laboratory III class. The study was conducted with 79 pre-service science teachers. The participants in the control group (n = 38) participated in traditional laboratory activities, and the participants in the experimental group (n = 41) participated in laboratory activities based on argument-driven inquiry. Data was collected through the Optical Achievement Test (OAT), Argumentative Scale (AS), Science Process Skills Test (SPST) and the individual reports of the participants. Qualitative and quantitative techniques were used together to analyze the data. The results showed that argument-driven inquiry was more effective in improving the academic achievement and science process skills of pre-service science teachers compared to traditional laboratory instruction, but no significant difference was observed in the Argumentative Scale scores between the groups that had ADI instruction and those that had traditional laboratory instruction. Towards the end of the treatment, there was an improvement in the argumentative quality of the experimental group, but there was no change in the argumentation quality of the control group. ADI is an effective method for improving the academic achievement and science process skills of students, and it could be adapted for other laboratory classes. Argumentativeness might be improved with a longer argumentation session and more laboratory activities.