Following severe anthropogenic pressure from rapid economic development, wetland biodiversity is now decreasing alarmingly, thus leading to adverse effects. Protected areas (PAs) can be crucial conservation tools to secure wetland biodiversity. However, whether these PAs exhibit high conservation efficiency in buffering wildlife and habitats from human pressures needs to be understood. Given their sensitivity to habitat quality and regional resource changes, threatened waterfowl could be suitable wetland ecosystem indicators. This study examined the conservation effectiveness of Henan Yellow River Wetland National Nature Reserve (HYRWNNR), which is a crucial region on the East Asia–Australia route for global bird migration. We performed Maximum Entropy (MaxEnt) modeling based on field survey data of the 19 threatened waterfowl species, and Human Impact Index (HII) was further mapped with waterfowls distribution to identify the conservation gap and priorities of the HYRWNNR. The results indicated that threatened waterfowl distribution were affected by both environmental factors and human pressure, and a conservation gap existed in the HYRWNNR. Two conservation scenarios were generated based on the spatial pattern of conservation priorities, and their corresponding management strategies were suggested. This study identifies conservation priorities from a novel perspective by synthesizing habitat suitability and human pressure, which can present basic information regarding the HYRWNNR management while supporting waterfowl conservation planning, ultimately promoting wetland habitats sustainability.