This study adopted an empirical analysis to explore social resilience to major natural disasters along the Tea-Horse Road (THR) in southwest China and to understand why and how the THR and its connected communities maintained and developed over a long period. A set of archive data, literature re-analysis, statistical data, monitoring data, and surveyed materials were collected and qualitatively and quantitatively analysed to support a holistic investigation of disaster impacts and social resilience. The results indicate that (a) natural disasters occurred frequently but were distributed over place and time and had various impacts, which left possibilities for maintaining social development with diverse and specific coping strategies; (b) strong central and local governance continually improved infrastructure and engineering technologies, and collaboration in social networks with local experience and disaster cultures were the major contributing factors that enhanced social resilience at various levels; (c) the THR area demonstrated various features of social resilience to natural disasters in terms of spatial-temporal scales, where the combination of multiple resilience measures enabled the resilience of the entire social system at various places over long time periods. Generally, larger social systems with diverse response capabilities were more resilient than small and individual entities over a long time scale. The study highlights that the THR region withstood frequent natural disasters but maintained a general development of social economy, transportation, and advanced technologies, and performed a positive transformation to a more resilient status. Overall, this paper describes the scale effects of multiple resilience measures along the THR and calls for specific studies on social resilience and transformation of diverse social entities over multiple spatial-temporal scales.