Grain structure and macrosegregation are two important aspects to assess the quality of direct chill (DC) cast billets, and the phenomena responsible for their formation are strongly interacted. Transient modeling of grain structure and macrosegregation during DC casting is achieved with a cellular automaton (CA)−finite element (FE) model, by which the macroscopic transport is coupled with microscopic relations for grain growth. In the CAFE model, a two-dimensional (2D) axisymmetric description is used for cylindrical geometry, and a Lagrangian representation is employed for both FE and CA calculations. This model is applied to the DC casting of two industrial scale Al-6.0 wt % Cu round billets with and without grain refiner. The grain structure and macrosegregation under thermal and solutal convection are studied. It is shown that the grain structure is fully equiaxed in the grain-refined billet, while a fine columnar grain region and a coarse columnar grain region are formed in the non-grain-refined billet. With the increasing casting speed, grains become finer and grow in a direction more perpendicular to the axis, and the positive segregation near the centerline becomes more pronounced. The increasing casting temperature makes grains coarser and the negative segregation near the surface more pronounced.