Reclaimed water irrigation can alleviate water resource pressure, while soil tillage is a common agricultural practice to increase crop yield. However, both of these practices may lead to the propagation of antibiotic resistance genes (ARGs). To date, there has been little research that has systematically investigated this issue. To fill this gap, this study has conducted microcosmic experiments to reveal the effect and mechanisms of using reclaimed water for irrigation and tillage treatment on the propagation of ARGs in soil, by utilizing high-throughput sequencing-based metagenomic assembly analysis approaches. The results showed irrigation significantly enhanced the abundance and diversity of ARGs in the soil. Compared to the initial soil, the total coverage of ARGs in the irrigated soil increased by 14.0 % (without tillage) to 22.7 % (with tillage). In particular, tillage treatment facilitated the enhancement of antibiotic resistome in the environment. The analysis with null model suggested soil tillage enabled ecological drift (52.4 %-66.7 %) to dominate the ARGs. Quantitative source apportionment using a machine learning-based microbial source tracking tool showed the irrigation exhibited considerable effect on the ARGs in the soil, with an average contribution of about 13.3 %-17.0 %. Network analysis revealed a close association of ARGs with mobile genetic elements (MGEs) and virulence factors, indicating potential dissemination risk of ARGs in the soil. Microbial communities, MGEs, and environmental factors collectively shaped the ARGs in the environment. Relatively, soil tillage enhanced the complex and stability of network structure and led to the colonization of ARGs in modular manner, resulting in higher contribution of ecological drift to soil resistome. Findings of this study will contribute to the management of resistome risks in reclaimed water utilization and agricultural activities for protecting soil ecosystem safety and public health.