The interaction between the minerals in a goethitic iron ore (goethite, quartz, hydrohematite, quartz-dispersed hydrohematite, and quartz-dispersed goethite) and pure flux materials (CaO, MgO, SiO2, and Al2O3) was studied by heating ore–flux interaction couples to different temperatures under 0.5 kPa O2 partial pressure when the samples were loaded into the hot zone of a furnace preheated to 1300 °C. The results show that CaO was the most effective flux for liquid-phase generation during sintering. MgO diffused into ore grains by solid-state diffusion and formed solid solution (Fe, Mg)O·Fe2O3, but did not generate liquid. Al2O3 and SiO2 in the interaction couples were relatively inert during heating. The goethite matrix, as the major mineral phase of the ore, played a key role in the interaction with CaO. At 1200 °C, no apparent liquid formation was observed. CaO diffused into the goethite matrix, and first reacted with SiO2 to form CaO·(SiO2)x. Then CaO combined with Fe2O3 and formed CaO·(Fe2O3)x. When heated to 1225 °C, CaO·(Fe2O3)x and CaO·(Fe2O3)x ·(SiO2)y phases formed by solid-state reaction started to melt. With increasing temperature, more liquid phase was generated. Whole ore particles were almost completely assimilated, with only a few dense ore fragments being observed in the samples heated to 1300 °C. Other mineral phases in the goethitic ore were less reactive due to their dense structure. On heating during sintering, dehydration of goethite generated a porous structure and cracks in the ore body, facilitating the diffusion of flux and penetration of flux-containing liquid phase. The core particles in the ore body, including hydrohematite minerals, remained relatively dense and so their assimilation during sintering is slow.