The human-land relationship in the affected area of the middle and lower reaches of the Yellow River is complex, and it is affected by overlapping natural and human activities. Clarifying the ecological space of the region and its ecological changes is of great significance to achieve the national strategy of ecological protection and high-quality development for the Yellow River Basin. In this study, we made a quantitative analysis on the evolution of ecological pattern and ecological status in the affected area of the middle and lower reaches of the Yellow River. Specifically, by analyzing the spatio-temporal evolution of ecological space with the data of land use and Remote sensing ecological index (RSEI) derived by remote sensing products, this study completely depicted the dynamic change pattern of ecological environment in the affected area of the middle and lower reaches of the Yellow River from 2000 to 2020. The results showed that:(1) from the perspective of the land use change, the main land use type in the study area was cultivated land, accounting for 70% of the study area. Over the past 20 years, cultivated land and construction land changed significantly. The area of cultivated land decreased by 2.15% (9849km²), and the construction land increased by 30.75% (11146km²), and the expansion of construction land was mainly by occupying cultivated land. (2) In terms of the ecological space, the areas of semi-ecological land changed greatly, mainly to weak-ecological land, which occurs in urban areas. The ecological space type in the coastal areas of Tianjin, Hebei, and Shandong changed from weak-ecological land to ecological land. The transition from semi-ecological land to ecological land appeared obviously in the Henan section of the Yellow River Basin. (3) For the RSEI, the area proportion with low level RSEI decreased from 38.85% in 2000 to 23.01% in 2020 while the area proportion with high level RSEI increased from 45.54% to 73.71% in recent 20 years. Relatively good ecological environment was mainly distributed around Henan, Jiangsu, and Anhui. The eco-environmental quality inside and outside the Yellow River beach area was similar, showing a slow upward trend. In this study, ecological space and its corresponding ecological status in the affected areas of the middle and lower reaches of the Yellow River were monitored and evaluated over a long time series based on the remote sensing big data, which provided the foundation support for the overall cognition and characterization for the ecological dynamics of the study area.