Schadow was trained under the court sculptor Jean-Pierre-Antoine Tassaert and in Rome (1785–87), where he studied under Antonio Canova. In 1788 he succeeded Tassaert as director of the Prussian royal school of sculpture in Berlin. His first monumental work was the tombstone for Count Alexander von der Mark (1790), in which he portrayed the nine-year-old count as a sleeping shepherd boy. His best-known work is the “Quadriga of Victory” (1793), a statue of a chariot drawn by four horses, atop the Brandenburg Gate. Among his finest works is the group of the princesses Luise and Friederike of Prussia (1797).

In later years Schadow's sight was affected and he turned more and more to writing on art theory. One of his sons, Rudolf Schadow (1786–1822) was also a sculptor, and another, Wilhelm von Schadow-Godenhaus (1788–1862), became well known as a painter.