Henan Province is an important ecological barrier in the middle and lower reaches of the Yellow River. It is of great significance to study its ecosystem quality and the driving mechanisms behind this in order to realize ecological conservation and high-quality development in the Yellow River Basin. In this study, from the perspective of physical elements, socioeconomic elements, and policy adjustments, multi-source data on land use, population density, forestry engineering, and other indicators were selected to construct an index system of the driving factors of ecosystem quality in Henan Province. The characteristics of spatio-temporal change and the formation mechanism of ecosystem quality in Henan Province from 2010 to 2020 were analyzed by comprehensively using the gravity center analysis method and a geo-detector tool. The results showed the following: (1) The ecosystem quality of Henan Province in 2020 has increased by 27.7% compared with that in 2010, and the center of gravity of ecosystem quality continued to move to the northwest of Henan Province. The quality of ecosystems in the hilly region of Western Henan, Tongbai, and Nanyang was better than that in the northern Loess Platform Hilly Area and the Yellow River Plain, and it presented a spatial pattern in which the quality of the south was higher than that of the north, while the east and west were equal; (2) From 2010 to 2020, the average GDP and population density in Henan Province were the most important factors affecting the quality of its ecosystem. The effect of land-use diversity on ecosystem quality in the hilly region of Henan Province was stronger than that in the central and eastern plains; and (3) The interactions among the driving factors were mainly nonlinear enhancement and double factor enhancement, in which the interaction between socio-economic elements and natural environmental elements was the dominant interaction mode and could enhance the impact on the quality of the regional ecological environment. The results of this study indicate that attention should be paid to generating targeted industrial economy layout and land use policies in different natural domains. Moreover, forestry protection engineering policies should be further strengthened to improve the resilience of ecosystem quality to human activities. © 2022 by the authors.