National Key Ecological Functional Areas (NKEFAs) play an important role in forestry restoration, water source conservation, soil and water conservation, windbreak and sand fixation, and biodiversity maintenance. They are the strategic core of ecosystem protection and restoration projects, not only directly related to ecological environment construction, but also profoundly affecting the sustainable development capacity of regional economy. This article selects 1256 ecologically and economically representative counties in China with complete data as research objects. Based on the data of the selected counties from 2007 to 2021, the entropy weight TOPSIS method is used to construct an economic resilience index, and a multi-period difference-in-differences (DID) model is adopted to explore the specific impact of the establishment of national key ecological functional areas on China’s economic resilience. Research has shown that national key ecological functional areas can enhance the resilience of county-level economies by promoting economic agglomeration and factor agglomeration, increasing fiscal expenditure and investment levels, and promoting sustainable development of county-level economies. The establishment of national key ecological functional areas in economically underdeveloped areas has had a positive effect on economic resilience, and the establishment of water source conservation, soil and water conservation, and biodiversity maintenance ecological functional areas has a significant impact on economic resilience. Therefore, national key ecological functional areas have generally promoted the improvement of China’s economic resilience, but in the process of policy implementation, the establishment of national key ecological functional areas should be promoted according to local conditions. This article not only provides empirical evidence for the effectiveness of China’s national key ecological function areas policies, but also provides methodological inspiration for formulating more precise and scientific ecological protection policies, which has reference significance for the implementation of similar policies in other regions around the world.