To elucidate austenite grain coarsening and mixed-grain formation in continuously cast Nb–Ti microalloyed steel during high-temperature holding, high-temperature holding experiments, Clyne–Kurz microsegregation calculations, Thermo-Calc equilibrium precipitation analysis, Gladman pinning calculations, and multi-order-parameter phase-field simulations were combined to investigate the effect of precipitation differences between dendritic and interdendritic regions on heterogeneous austenite grain growth. The experimental results show that mixed-grain structures of varying severity are present after holding for 1 h at 1050–1300 °C. The austenite grains coarsen overall with increasing temperature, while pronounced coarsening of the initially fine-grained regions occurs above approximately 1200 °C. Microsegregation calculations suggest that Nb, Ti, and C are enriched in the interdendritic region, which may promote higher Nb(C,N) and TiN precipitation compared with the dendritic region. As temperature increases, grain-boundary mobility increases continuously. At 1150 °C, a considerable amount of precipitates remains in the interdendritic region, whereas pinning in the dendritic region is weaker, causing the difference in effective grain-boundary mobility between the two regions to increase. At higher temperatures, extensive dissolution of interdendritic Nb(C,N) reduces the regional difference in pinning and, consequently, the difference in effective grain-boundary mobility. The phase-field simulations capture the general characteristics of heterogeneous austenite grain-growth behavior and provide mechanistic insight into the influence of spatially varying effective grain-boundary mobility: at 1050 °C, low grain-boundary mobility and strong pinning result in slow grain coarsening; near 1150 °C, preferential growth in the dendritic region while the interdendritic region remains pinned produces the highest mixed-grain severity; at 1300 °C, extensive precipitate dissolution causes pronounced overall grain coarsening while reducing the regional grain-size contrast. The experimental observations were further interpreted using microsegregation and precipitation calculations to reveal the possible relationship between solidification-induced compositional heterogeneity and heterogeneous grain growth. These results indicate that local variations in effective grain-boundary mobility associated with solidification microsegregation are an important factor influencing the formation of mixed-grain structures.