It depicts the battle of Issus (333 BC) between Alexander the Great and Darius III of Persia. Alexander defeated the Persian army, and his strength is clearly visible in the mosaic, which portrays Darius with a fearful facial expression.
Despite being partially ruined, the two main figures are easily recognizable. The portrait of Alexander is one of his most famous ones, and the whole scene is very vivid.
Apparently the mosaic is a copy of a fresco from the fourth century BC, by the painter Philoxenos of Eretria.