The son of a stained-glass painter, Goltzius was taught that art by his father and was then instructed in copperplate engraving by Dirck Volckertszoon Coornhert in Haarlem. Goltzius' marriage to a rich widow in 1579 enabled him to set up an independent business in Haarlem, where he spent the rest of his life except for a tour of Germany and Italy in 1590. Owing to his technical facility, he developed into one of the great masters of engraving in Holland. His earliest works were reproductions of prints by Albrecht Dürer, Lucas van Leyden, and others, some so skillful as to be mistaken for the originals. He also began designing his own compositions, among them a set illustrating the “Story of Ruth and Boaz” and another depicting the “Story of Lucretia,” the ravished Roman matron. These early works feature intricate detail and interesting chiaroscuro effects of light and shade. Goltzius' series of “Roman Heroes” (1586) is executed in a broader manner, as is the series of large prints on the life of Christ he did in the 1590s, in which he imitated the styles of various Italian and Dutch Renaissance artists. Among his best-known prints are the engraving of the “Farnese Hercules” and the chiaroscuro woodcut of “Hercules Killing Cacus.” His miniature portraits are distinguished both by their finish and as studies of character.

In his technique as an engraver Goltzius is considered unsurpassed, even by Dürer (Dürer, Albrecht); his Mannerist eccentricities and extravagances are counterbalanced by the freedom and virtuosity of his execution. He began painting late in the 1590s in the Mannerist style, but his work in that medium is unimpressive.