Abstract: 69 groups of water samples were collected for investigation on concentration of As, Cu, Cd, Zn, Pb and Mn to expose the pollution status in the mainstream of the Yellow River, from Baiyin City in Gansu Province to Shapotou City in Ningxia Hui Autonomous Region. Heavy metal pollution index, Nemero index and potential ecological risk assessment model were employed to evaluate the pollution characteristics and potential ecological risk in this stream section, and pollutant sources were also analyzed based on the distribution of industrial and agricultural activities by Pearson correlation analysis and principal component analysis. The results show that Class Ⅱ criteria of national surface water quality standard was matched by As, Cu, Cd, Zn and Pb but exceeded by Mn component with increasing tendency of all heavy metal content along the river, and high content samples were mostly found in or near the tributaries confluence. The assessment results demonstrate that pollution level of this river section is very slight pollution level by heavy metal pollution index, relatively clean to heavy pollution level by Nemero index and slight ecological risk level by both single and multi-element comprehensive potential ecological risk index. As, Cu and Mn pollutants are recognized as mainly composite pollutants from industrial and natural sources, Cd and Pb are mainly influenced by the combination of agricultural and industrial activities, and Zn is mainly from traffic source. Human activity is the key factor affecting the water quality in the study area.