[Objective] The response law for runoff under different land use scenarios in the middle and upper reaches of the Weihe River was analyzed in order to provide scientific support for development planning and water resource management of the middle and upper reaches of the Weihe River. [Methods] Based on land use data from 1980 to 2020, the characteristics of land use change in the Weihe River basin over the past 40 years were analyzed. the SWAT model was used to set up five historical land use scenarios, two comprehensive land use scenarios, and three extreme land use scenarios in order to determine the response of runoff under different land use scenarios. [Results] ① During the past 40 years, the areas of cultivated land, water, and unused land gradually decreased, while the areas of forest land, grassland, and residential land gradually increased. ② From 1980 to 2020, the simulated annual average runoff depths were 72.24, 72.27, 72.31, 71.86 mm, and 72.25 mm in five periods, respectively. The average annual runoff depths were 68.59 mm, 69.70, 72.60, 64.81, and 66.82 mm, respectively. [Conclusion] The SWAT model had good adaptability for the middle and upper reaches of the Weihe River. The impact of land use type changes on runoff in the middle and upper reaches of the Weihe River was less than 10%. Returning farmland to forest and grassland was mainly responsible for inhibiting runoff. In the three extreme land use scenarios, runoff size followed the order of cultivated land type＞grassland type＞forest type, and the differences between cultivated land and forestland and grassland were obvious.