The Yellow River Delta National Nature Reserve, located at the estuary of the Yellow River in Shandong Province, was closely linked to the health of the Yellow River basin's ecosystem. Investigating its ecological conditions was of great significance for promoting regional sustainable development and achieving national ecological protection strategy goals. This study employed the Ecological Grade Index (EGi, a negative indicator), which characterized the ecological condition, in conjunction with the Theil-Sen median method and the Mann-Kendall test, to study the spatial-temporal variations in the ecological condition of the reserve from 2000 to 2020. Additionally, we used the Geographical Detector to analyze the driving factors and employed the Hurst exponent to predict future trends based on the spatial-temporal variations information. The MaxEnt model was also utilized to analyze the suitable habitat areas for birds. The results indicated: (1) The ecological condition of the study area was spatially distributed with better conditions along the coast and near river channels, and poorer conditions inland. (2) Between 2000 and 2020, the EGi showed a fluctuating downward trend, while the ecological condition gradually improved. The trend of ecological condition changes was dominated by improvement, with an area proportion of 71.50%. Areas showing degradation trends and stable conditions were relatively small and mainly distributed in the southeastern coastal zone of the southern region. (3) The driving factors, ranked from highest to lowest in terms of their explanatory power for ecological conditions, were: temperature, elevation, population, precipitation, Normalized Difference Vegetation Index, and Gross Domestic Product, with the most significant interaction occurring between temperature and Normalized Difference Vegetation Index. (4) The overall development trend for the future of the study area was positive. (5) The suitable habitats for birds were mainly distributed in the central part of the southern region and were consistent with areas of better ecological conditions. They were primarily located in the narrow zones along the Yellow River and the coastal areas, presenting a belt-like distribution. Elevation, NDVI, and land use types were the factors that contributed the most to the spatial distribution of bird suitable habitats, with average contribution rates of 35.1%, 22.6%, and 15.5%. To effectively protect the ecological environment of the reserve, future efforts must focus on strengthening management of the Yellow River channels and the wetlands on both sides of it, strictly regulating human activities, and implementing regular bird monitoring and ecological assessment. Through scientific planning and rigorous management, efforts will be intensified to promote harmonious coexistence between bird species and their ecological environment, providing strong support for the ecological protection and high-quality development of the Yellow River Delta.