Rapid urbanization and industrialization have greatly contributed to boosting regional economic growth and mitigating the problem of poverty, but blind expansion of cities and towns has not only caused the inefficient use of urban land resources but also caused the deterioration in the urban ecological environment. Within the current context of emphasizing high-quality development, achieving synergy between the efficient use of urban land and ecological environmental protection is an urgent task for promoting new urbanization construction. In this study, cities in the upper reaches of the Yangtze River (URYR) were adopted as the research object, a theoretical analysis framework for the urban land use efficiency (ULUE) and ecological environment quality (EEQ) was established, the ULUE was measured by using the Slacks-Based Measure (SBM) model, the coupling coordination and interactive corresponding response relationship between the ULUE and EEQ were analyzed, and the influencing factors of the coupling coordination between these two systems were explored by using the random forest model. The following conclusions can be obtained: in 2020, compared with those in 2006, both the ULUE and EEQ were improved, and the two systems exhibited interactions and significant spatiotemporal heterogeneity. The coupling coordination degree (CCD) between the ULUE and EEQ could facilitate maintaining the original state, and the transfer of the CCD exhibited a significant spatial correlation with the state of neighbouring cities. The effect of the ULUE on the EEQ indicated nonlinear characteristics, while the effect of the EEQ on the ULUE was manifested as inhibition initially and then promotion. The random forest regression results showed that the population density, landscape agglomeration and connectivity, market conditions, government intervention, and industrial institutions are the key influencing factors of the CCD. Finally, this study provides policy implications for innovative urban land use modelling, environmental regulation, and industrial transformation and upgrading.