Currently the deteriorated water quality for Huaihe River Basin (HRB) in China was still serious because of the negative influence multiple pollution sources including animal manure. However, little attention was paid to the potential risk of animal manure for farmland and water quality of HRB. This study was quantified and forecasted animal manure risk and its spatiotemporal variations in HRB from 2008 to 2018, through pollution discharge coefficient method and pollution load calculation, combined with kriging interpolation method of ArcGIS technology, based on statistics principle. All the data were originated from livestock and poultry breeding in HRB from 2008 to 2018. The future risk of farmland and water environment in HRB was further forecasted. The results indicated that the livestock and poultry manure has become a key pollution source causing a negative influence on farmland and water quality owing to a large amount of animal manure production without efficient recycle utilization. The chemical oxygen demand (COD) and total nitrogen (TN) discharge of animal manure in HRB almost accounted for 17.00% and 39.00% of the whole COD and TN discharge in China. The diffusion concentration of TN and TP in those regions of Shangqiu, Zhoukou, Heze, Zhumadian, Luohe, Jining, Xuchang, Kaifeng, Taian and Zhengzhou of HRB has exceeded the threshold value 10.00 mg/L of TN and 0.08 mg/L of TP, causing water eutrophication and cancer villages. The assessment of farmland and water quality risk revealed that Zhumadian, Zhoukou, Shangqiu, Taian, Jining, Heze, Linyi and Rizhao belonged to high risk areas in HRB, which were still obtained high farmland and water quality risk index in 2030. The results provided insight into an important significance of sustainable balance of livestock and poultry development and ecosystem in HRB.