Abstract: In view of the increasingly severe ecological landscape stress in the Pearl River Delta region caused by the accelerated urbanization process, it is urgent to strengthen regional ecological protection. A coupling and coordination model between new urbanization and landscape ecological security was constructed, and the spatiotemporal pattern and development status of urban spatial expansion and landscape ecological security coupling and coordination in the Pearl River Delta region from 2000 to 2020 were quantitatively measured. The driving mechanism was revealed by using multiple regression analysis and a grey prediction model, and the development trend of urban spatial expansion and landscape ecological security coupling in 2040 was predicted. The results showed that: 1) The coupling coordination degree between urbanization and landscape ecological security in nine cities in the Pearl River Delta had shown a slow fluctuating upward trend over the 20 years, with the range of coupling coordination degree increasing from 0.305-0.436 in 2000 to 0.385-0.545 in 2020. It was currently in the antagonistic coupling stage, and would continue to move towards coordinated, synchronized, and orderly development in the next 20 years. 2) The economic development in the Pearl River Delta was unbalanced, and urban development and ecological environment protection were difficult to develop simultaneously. The landscape ecological situation was not optimistic, the number of cities with a lagging ecological environment was increasing, and a good coordinated development had not yet been fully formed. 3) The degree of openness, level of economic development, and investment in science and education funds had a significant impact on the coupling coordination degree (P<0.05). In the future, it is necessary to strengthen the research on the mechanism of coupling and coordination for regional sustainable development and continue to pay attention to the trend and characteristics of coordinated development between urban spatial expansion and landscape ecological security.