Direct-chill (DC) cast billets 192 mm in diameter of an Al-Cu-Mg alloy were examined in detail with the aim to reveal the effects of grain refining (GR) and casting speed on structure, “floating” grains, and centerline macrosegregation. Experimental results show that grain size and dendrite arm spacing (DAS) tend to coarsen toward the billet center with a local refinement DAS in the center. In GR billets, grain size does not change much with the cooling rate, casting speed, and grain refiner amount. Coarse-DAS (floating) grains are observed around the billet axis regardless of GR and the amount of Ti, though their amount is significantly higher in GR billets. Macrosegregation profiles show a negligible influence of GR, while the effect of casting speed is large. The concept of solute-depleted floating grains contributing to the centerline macrosegregation is substantiated by microsegregation measurements, which show that, independent of GR, coarse dendrite branches have a depleted concentration plateau in contrast to the fine dendrite arms.