Nature-based solutions (NbS) - working with and enhancing nature to address societal challenges - are increasingly being featured in climate change adaptation policy and plans. While there is growing evidence that NbS can reduce vulnerability to climate change impacts in general, there is a lack of understanding on the mechanisms through which this can be achieved, particularly in the Global South. To address this, we analyse 85 nature-based interventions in rural areas across the Global South, and factors mediating their effectiveness, based on a systematic map of peer-reviewed studies encompassing a wide diversity of ecosystems, climate impacts, and intervention types. We develop and apply an analytical framework of people’s social-ecological vulnerability to climate change, in terms of six pathways of vulnerability reduction: social and ecological exposure, sensitivity, and adaptive capacity. Most cases (95%) report a reduction in vulnerability, primarily by lowering ecosystem sensitivity to climate impacts (73% of interventions), followed by reducing social sensitivity (52%), reducing ecological exposure (36%), increasing social adaptive capacity (31%), increasing ecological adaptive capacity (19%) and/or reducing social exposure (14%). An analysis of mediating factors shows that social dimensions are equally important as technical factors in NbS to achieving equitable and effective outcomes. Attention to the distinct social and ecological pathways through which vulnerability is reduced helps to harness the multiple benefits of working with nature in a warming world.