[Objective] The correlation between land use changes and ecosystem service values were assessed to provide references for formulating appropriate land intervention policies.[Methods] The five-period land use data of the Irtysh River basin and the CLUE-S model were used to quantify the temporal and spatial variation of ecosystem service value profit and loss under land use change.[Results] ① The conversion of grassland and forest land to other land continued from 2000 to 2018 in the Irtysh River basin, and the cultivated land area increased significantly. By 2030, the proportion of arable land in this basin would increase by 4.92% (from 1 502.48 km² to 4 070 km²), while the forest land area decreased rapidly by 7.18% (from 7 547.26 km² to 5 424.36 km²). ② The value of ecosystem services in the Irtysh River basin increased from 51.816 billion yuan in 2000 to 183.244 billion yuan in 2018. By 2030, the value of ecosystem services would be in a fluctuating downward trend (177.786 billion yuan in 2030). ③ Forest land and grassland were converted to cultivated land, and the resulting loss in ecosystem service value in the Irtysh River basin was expected to reach 10.880 billion yuan, followed by grassland conversion loss (3.439 billion yuan) > forest land conversion loss (2.849 billion yuan) > water area conversion loss (1.831 billion yuan). ④ The spatial distribution of ecosystem service value gains and losses in the Irtysh River basin showed a pattern of "high in the north and low in the south", and the value gains and losses showed positive spatial autocorrelation, both globally and locally.[Conclusion] Human factors led to the occupation of a large amount of ecological land, a decline of ecosystem service value, and significant spatial heterogeneity of profit and loss. It is necessary to undertake further effective ecological protection and compensation policies to promote the livelihood transformation of farmers and herdsmen, and to reduce their dependence on the natural environment.