The Human Appropriation of Net Primary Production (HANPP) of agroecosystems is critical to food security, sustainable cropland use, and key biogeochemical processes such as carbon cycling and energy flow. However, current agroecosystem management lacks the support of high-resolution crop-type-specific HANPP information. To this end, this study integrated multi-source data of crop type, Normalized Difference Vegetation Index (NDVI) time-series, irrigation and climate, and multiple methods of the Miami model, the Carnegie-Ames-Stanford Approach (CASA) model, and process parameters to map the 30-m resolution spatial distribution of agroecosystem HANPP in the Heihe River Basin (HRB) in 2007 and 2012. We then analyzed the influences of climate condition, irrigation, and crop type on the HANPP. The average HANPP in the HRB decreased from 762.4 to 712.1 g C/m2 from 2007 to 2012, with a decrease by 6.6%. The HANPP values of wheat, barley, and oilseed rape decreased by more than 10.0%, whereas that of corn only decreased by 3.1%. The ratio of HANPP to potential NPP (NPPpot) dropped from 82.7% to 81.4% and that of land-use-induced HANPP (HANPPLUC) to HANPP from 61.9% to 58.5%, whereas that of crop-harvest-induced HANPP (HANPPharv) to HANPP increased from 38.1% to 41.5%. These changes indicated that crop productivity increased whereas NPP loss decreased. Crop type conversion accounted for 84.7% of the HANPP changes in HRB, with a value of −93.6 × 109 g C. Due to irrigation supplementation, the HANPP in high-temperature areas was higher than that in low-temperature areas with high precipitation. However, irrigation above 1000 mm no longer promoted HANPP, indicating that the irrigation efficiency in the HRB is low. Reducing HANPPLUC and carbon-water inputs while increasing HANPPharv is the key approach to obtain food security and sustainable agroecosystem development. Effective irrigation strategies and scientific crop planting adjustment should take into account their spatially heterogeneous and crop-specific impacts on the HANPP to help achieve these goals.