Qinghai Lake is the largest saline lake in China. The change in the lake volume is an indicator of the variation in water resources and their response to climate change on the Qinghai-Tibetan Plateau (QTP) in China. The present study quantitatively evaluated the effects of climate change and land use/cover change (LUCC) on the lake volume of the Qinghai Lake in China from 1958 to 2018, which is crucial for water resources management in the Qinghai Lake Basin. To explore the effects of climate change and LUCC on the Qinghai Lake volume, we analyzed the lake level observation data and multi-period land use/land cover (LULC) data by using an improved lake volume estimation method and Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model. Our results showed that the lake level decreased at the rate of 0.08 m/a from 1958 to 2004 and increased at the rate of 0.16 m/a from 2004 to 2018. The lake volume decreased by 105.40×108 m3 from 1958 to 2004, with the rate of 2.24×108 m3/a, whereas it increased by 74.02×108 m3 from 2004 to 2018, with the rate of 4.66×108 m3/a. Further, the climate of the Qinghai Lake Basin changed from warm-dry to warm-humid. From 1958 to 2018, the increase in precipitation and the decrease in evaporation controlled the change of the lake volume, which were the main climatic factors affecting the lake volume change. From 1977 to 2018, the measured water yield showed an “increase-decrease-increase” fluctuation in the Qinghai Lake Basin. The effects of climate change and LUCC on the measured water yield were obviously different. From 1977 to 2018, the contribution rate of LUCC was –0.76％ and that of climate change was 100.76％; the corresponding rates were 8.57％ and 91.43％ from 1977 to 2004, respectively, and –4.25％ and 104.25％ from 2004 to 2018, respectively. Quantitative analysis of the effects and contribution rates of climate change and LUCC on the Qinghai Lake volume revealed the scientific significance of climate change and LUCC, as well as their individual and combined effects in the Qinghai Lake Basin and on the QTP. This study can contribute to the water resources management and regional sustainable development of the Qinghai Lake Basin.