The transformational potential of the United Nations’ 2030 Agenda for Sustainable Development Goals (SDGs) lies in effective efforts to reconcile the conflicts and maximize the synergies among the interrelated SDGs. Previous research on the interrelationships among SDGs often focused on depicting the degree to which different goals reinforce or hamper each other; however, drivers behind these interrelationships have rarely been evaluated. We developed a novel approach to unraveling the impact of human activities on the complex trade-offs and synergies among SDGs. We used the approach to assess the impacts of four globally common livelihoods, including cropping, local off-farm labor work, labor migration, and livestock husbandry, on the interrelationships among SDG 1 (no poverty), SDG 3 (enhance human well-being), and SDG 15 (protect life on land) in a demonstration site. The results show that our approach can be very useful in informing coherent governance and facilitating progress toward SDGs across social, economic, and environmental dimensions simultaneously.