Carl Von Piloty was born in Munich.

His father, Ferdinand Piloty (d. 1844), enjoyed a great reputation as a lithographer.

In 1840 he was admitted as a student of the Munich Academy, under the artists Schorn and Schnorr. After a journey to Belgium, France and England, he commenced work as a painter of genre pictures, and in 1853 produced a work, Die Amme (“The Wet Nurse”), which, on account of its originality of style, caused a considerable sensation in Germany at the time.

But Carl Von Piloty soon forsook this branch of painting in favour of historical subjects, and produced in 1854 for King Maximilian II The Accession of Maximilian I to the Catholic League in 1609. It was succeeded by Seni at the Dead Body of Wallenstein (1855), which gained for the young painter the membership of the Munich Academy, where he succeeded Schorn (his brother-in-law) as professor.

Among other well-known works by Carl Von Piloty are the Battle of the White Mountain near Prague, Nero Dancing upon the Ruins of Rome (1861), Godfrey of Bouillon on a Pilgrimage to the Holy Land (1861), Galileo in Prison (1864) and The Death of Alexander the Great (unfinished), his last great work. He also executed a number of mural paintings for the royal palace in Munich.

In 1874 he was appointed keeper of the Munich Academy, being afterwards ennobled by the king of Bavaria. Piloty was the foremost representative of the realistic school in Germany.

He was a most successful teacher, and among his more famous pupils may be mentioned Nikolaos Gyzis, Nikiforos Lytras, Georgios Jakobides and Constantine Volanakis.