Climate change has a major impact on the livelihoods, crop yields, and sustainability of agricultural systems for soybean farmers in Northern Ghana. Ecosystem-based approaches are still not widely adopted by soybean farmers in Ghana, despite several initiatives to promote climate-smart agriculture in the area. This research seeks to examine the ecosystem-based approaches used by soybean farmers, the climate variability status of farmers, and the ecosystem-based mitigation approaches of farmers. The study used a cross-sectional design and 280 farmers through a multistage sampling technique. The study result indicates that row planting and keeping weed-free farms were soybean farmers’ most used ecosystem-based approaches. The experience and effect of climate change had bidirectional significance and were influenced by sustainable agriculture practices and the intensity of agricultural technology use. Furthermore, experience with climate change and pest and weed management was significant in influencing ecosystem-based mitigation approaches used by farmers. The study shows that while ecosystem-based approaches are beneficial in addressing climate change, organizations such as the Environmental Protection Agency and Ministry of Food and Agriculture should provide more targeted support, education, and policy initiatives aimed at enhancing farmers’ adoption and effectiveness in mitigating climate variability and its associated challenges for soybean farmers in Northern Ghana.