Global sustainability initiatives are gaining momentum and impact, and place-based research can provide complementary insights to strengthen them. Here, we explore the current and potential role of place-based research into informing global sustainability initiatives by assessing the strengths, challenges, and opportunities. We show that place-based research allows for a better understanding of global social–ecological dynamics, and that transformations towards sustainability are often triggered at the local scale through the co-construction of local solutions. We discuss that the very nature of place-based research can hinder its transferability because its global integration faces temporal, spatial and governance scale mismatches, and we identify some of the key challenges of scaling-up its findings. We highlight new opportunities to mainstream place-based research that are emerging from first, long-term networks of place-based research, second, new institutional research settings that contribute with conceptual comprehensive frameworks and capacity building tools, third, a global community of practice, and fourth, the concept of region as a bridge between local and global sustainability initiatives. We believe that the time is ripe to promote the role of place-based social–ecological research as a key contributor to achieve global sustainability goals.