Innovation is an important motivating force for regional sustainable development. This study measures the innovation efficiency of 280 cities in China from 2014–2018 using the super-efficiency slack-based measure and it also analyzes its impact on the ecological footprint using the generalized spatial two-stage least squares (GS2SLS) method and uses the threshold regression model to explore the threshold effect of innovation efficiency on the ecological footprint at different economic development levels. We find the corresponding transmission mechanism by using a mediating effect model. The major findings are as follows. First, we find an inverse U-shaped relationship between innovation efficiency and the ecological footprint for cities across China as well as in the eastern and central regions. That is, innovation efficiency promotes then suppresses the ecological footprint. Conversely, in western and northeastern China, improvements in innovation efficiency still raise the ecological footprint. Second, for the entire country, as economic development increases from below one threshold value (4.4928) to above another (4.8245), the elasticity coefficient of innovation efficiency to the ecological footprint changes from −0.0067 to −0.0313. This indicates that the ability of innovation efficiency improvements to reduce the ecological footprint is gradually enhanced with increased economic development. Finally, the industrial structure, the energy structure, and energy efficiency mediate the impacts of innovation efficiency on the ecological footprint.

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