The rupture behavior of the modified 10Cr-1Mo steel multi-layer welded joint is determined by the fine-grain zones of the weld metal adjacent to the fusion line during the long-term creep test at 620 °C. The microstructures of multi-layer weld metal before and after the creep tests were characterized in detail, and its role in creep behavior was systematically investigated. Most grain boundaries of subgrains represented the low-angle boundaries in the weld metal adjacent to the fusion line both before and after the creep test. The widths of grains in the fine-grain zones were about 0.5-1 μm. The fracture morphology appeared as "wave" structure due to the cracking initiating from multi-layer grain boundaries in the fine-grain zones. Some W elements that melted into weld metal adjacent to the fusion line altered the thermodynamic and kinetic conditions of the Laves phase formation during long-term creep exposure. Laves phase particles mainly distributed along the grain boundaries due to the faster diffusion and segregation of Mo, W, and Si elements. Moreover, higher-density grain boundaries in the fine-grain zones led to easier nucleation and growth of Laves phase particles. Compared with other areas in the welded joint, the size of Laves phase particles in the fine-grain zones of the weld metal adjacent to the fusion line was the largest ones. The interface between Laves phase particles and the matrix acted as the nucleation site of creep micro-cavities. The creep micro-cavities grew up at the expense of fine-grain boundaries and even grew across the grain boundary deeply into adjacent grains, and then developed to cracks in the fine-grain zones.