Comprehensive monitoring and assessment of the ecological changes in the Yellow River Delta (YRD) is fundamental of properly understanding ecological conditions of the delta region and strengthening ecology and environment protection and supervision. Based on multi-source satellite remote sensing and ground observation data, this study monitored the changes of ecological space and vegetation growth in the High Efficiency Eco-economic Zone of the Yellow River Delta (HEEZ-YRD) over the past 30 years, identified the basic characteristics of regional ecological status, and quantitatively analyzed changes of regional wetland, coastline, water and sediment resources. Then, combining with a series of ecological protection and restoration measures taken by the state and local governments, this article discussed the regional protection effectiveness, identified the main ecological problems in the YRD, and put forward countermeasures and suggestions. The results show that from 1990 to 2018, occupied by urban and agricultural space, the reduction of ecological spatial area in the past 30 years was about 7.6% of that in 1990, and the growth trend of vegetation around the coastal and urban agglomeration areas decreased in the HEEZ-YRD. Artificial wetland that mainly composed by ponds increased by 18.1%, artificial shoreline increased by 27.1%, and the natural wetland and shoreline resources lost significantly. The speed of ecological space being occupied has slowed between 2010 and 2018, and the positive effects of ecological protection planning and engineering measures have gradually emerged. The growth rate of the artificial wetland area and the artificial shoreline length has slowed significantly, and the regional ecological protection effect has gradually shown. Since the 1950s, water and sediment conditions of the Yellow River have changed dramatically, and the water and sediment resources entering the YRD have gradually reduced. The ecological water replenishment demand of the original wetland and the threat of erosion and regression faced by new wetland are still severe. Therefore, increasing protection and restoration of regional wetland resources, optimizing the spatial distribution planning of ecological protection, and strengthening the control of ecological space are the necessary means to improving the biodiversity of the YRD and promoting the high-quality development for the region.