Microplastics are widely found in rivers and their sediments, which will cause harm to the water ecological environment. The Wei River is a first-class tributary of the Yellow River, the fifth largest river in the world, and has vulnerable ecological environment and most sediment in the world. However, understanding how anthropogenic activities and environmental factors affect the microplastics distribution in this river is not clear. Based on this, the spatiotemporal distribution of microplastics in the Wei River were investigated. The abundance of microplastics ranged from 1033 to 8333 items/m3 and from 120 to 840 items/kg in the water and in the sediment, respectively. Fibers and fragments were the main shapes of Wei River, microplastics less than 500 μm were the main sizes, and black and white/transparent were the main colors. In Wei River, the abundance of microplastics in urban areas was higher than that in agricultural areas and mountainous areas. Furthermore, the correlation analysis revealed that microplastic abundance in the water was related to anthropogenic activities (population density, per capita GDP and distance) and environmental factors (water temperature, NH3-N, ORP), while in the sediments was correlated with anthropogenic activities (per capita GDP) and environmental factors (water temperature and NH3-N). This study reveals new patterns in microplastic pollution in the Wei River, underscoring the need for targeted environmental strategies. Our findings provide novel insights into the characteristics and distribution of microplastics, significantly adding to the current understanding of riverine microplastic pollution.