[Objective] Spatial-temporal changes of normalized difference vegetation index (NDVI) in the Yellow River basin were analyzed and its response mechanism to climate change and human activities was investigated in order to provide references for appropriate ecological engineering and guarantee ecological protection and high-quality development in the Yellow River basin.[Methods] In conjunction with MODIS NDVI, precipitation, and temperature data, we used unary linear trend analysis, Hurst index, partial correlation analysis, and residual analysis methods to analyze the spatial-temporal changes of NDVI in the Yellow River basin between 2000 and 2018. The NDVI's dual response mechanism to climate and human activities was discussed.[Results] ① NDVI in the Yellow River basin showed increased volatility over time with an overall growth rate of 6.8%/10 year. The NDVI was higher in the southeast and west, and lower in the north and northwest. The NDVI decreased from southeast to northwest. The NDVI was highest in the downstream region, intermediate in the midstream region, and lowest in the upstream region. NDVI also had a V-shaped distribution bounded by the East Asian monsoon eco-geographical area, the northwest arid eco-geographical area (Erdos-Maowusu Sandy Land-Qingyang-Pingliang-Dingxi), the Qinghai-Tibet Plateau eco-geographical area and zone bounded by the northwest arid eco-geographical area, and the East Asian monsoon eco-geographical area (Xining-Gannan-Dingxi); ② The overall trend of the NDVI showed improvement. Its anti-continuity was stronger than continuity with great weak continuity. The improvement area accounted for about 62.32% of the total area, and was distributed as a strip-shaped area in the middle and upper reaches of the Ordos-Mowsu Sandy Land-Qingyang-Pingliang-Dingxi-Xining-Gannan, Taiyuan Basin-Linfen Basin-Guanzhong Plain, and the zone bounded by Yuncheng Basin-Sanmenxia. The degraded areas were dominated by the middle and lower reaches with scattered distribution; ③ The NDVI was positively correlated with precipitation and air temperature, and the intensity of the partial correlation with precipitation was slightly larger than that of air temperature. The NDVI residuals in about 76.7% of the basin were increasing. The overall impact of human activities on NDVI was positive, and was greatest in the midstream region, followed by the upstream region, and finally the downstream region.[Conclusion] NDVI changes in the Yellow River basin are influenced by climate and human activities and exhibit spatial heterogeneity. Appropriate ecological engineering and agricultural production activities play an important role in vegetation restoration.