In 2003, an 8-storey reinforced concrete (RC) frame-supported masonry structure, located in Hengyang City, China, underwent a severe fire-induced collapse accident. Information on the structure and the fire scenario is presented. It includes the design data, the site observation record of the fire incident, and the laboratory material test results. Preliminary investigation reveals that about 45.9% of the bottom storey of the RC frame experienced temperatures in excess of 800°C, and its central area reached 1300°C. Such a severe fire load, of fairly high temperature and large area, is thought to be the primary cause of the progressive collapse of the entire building structure. To better understand the collapse mechanism, this study presents a coupled thermo-mechanical numerical simulation of the building collapse. The actual collapse area is well reproduced by the proposed numerical model. The simulation further demonstrates that the initial damage happened to two interior columns exposed to temperature of 1300°C. Such damage was also attributable to the large gravity load they carried, and the complicated nature of the local structural arrangements. The adjacent structural members were subsequently damaged, because they were also weakened by the fire, and were over-loaded by the redistributed load. Failure of the two interior columns and adjacent area eventually triggered a progressive collapse. Further, the effect of some critical factors on the collapse mechanism is discussed. On the basis of this numerical case study, practical design considerations on the key structural components, the fire compartments, and the structural robustness are given for the prevention of the fire-induced progressive collapse of RC frame structures.