Clarifying the spatial distribution of ecosystem services and service clusters in the mountain-river-sea coupling key zones is of great significance for regional ecological function management and ecosystem service capacity improvement. To assess the level of ecosystem services and the capacity of multiple ecosystem services in the southwestern Guangxi Karst-Beibu Gulf in 2018 through the InVEST model and multiple ecosystem services landscape index, and then to explore ecosystem service trade-offs/synergistic relationships and distribution patterns, and to identify the different service clusters through the self organizing feature map. The results showed that the multiple ecosystem service capacity of the mountain-river-sea coupling key zone was high, with the MESLI average of 1.65. The water yield and food production showed a distribution characteristic of decreasing from southeast to northwest, and MESLI and carbon storage and sequestration, soil conservation, habitat quality, and water quality purification services showed the distribution characteristics of low in the middle and high in the surrounding areas. As the topographic gradient increases, water yield and food production gradually decrease, and MESLI, carbon storage and sequestration, soil conservation, habitat qulaity, and water quality purification increased with the increase of topographic potential gradient. The ecosystem services were mainly synergistic with each other, and food production and carbon storage, habitat qulaity, soil conservation, and water quality purification were trade-offs, with the high trade-off areas mainly distributed in the key zone of Zuojiang River and Youjiang River basins and the key zone of Beibu Gulf coast. The mountain-river-sea coupling key zones can be divided into four categories, namely, ecological conservation, soil conservation, food supply, and human habitat bundles. Among them, the ecological conservation bundle has the largest distribution area and is mainly distributed in the mountainous areas of northwestern Karst key zone, and the areas of southeastern Shiwan Mountain and Liuwan Mountain, with the largest MESLI, while the habitat bundle is mainly distributed around the food supply bundle, with the smallest distribution area and the smallest MESLI. Therefore, the region needs to strengthen the ecological management and restoration of the habitat bundles, which is conducive to improving the multiple ecosystem service capacity of the mountain-river-sea coupling key zone, and promoting the coordinated and sustainable development of the region.