Some of Francois' early work in Brussels attracted the notice of the Archduke, who gave him the wherewithal to study in Rome, where he would spend his whole career.

According to early biographers, when Duquesnoy arrived in Rome in 1618, he studied antique sculpture in detail, climbing over the equestrian Marcus Aurelius to determine how it was cast, or making a pilgrimage to the shrine of Diana at Lake Nemi.

In 1624, Nicolas Poussin, who shared his classicly styled, emotionally detached manner of depiction, arrived in Rome, and the two foreign artists lodged together.

[4] In spite of the contrast perceived by contemporaries in their stylistic approaches, Duquesnoy collaborated with Bernini in the design, among others, of the angels offering garlands of the baldacchino for Saint Peter's (in process 1624–1633).

This is one of four sculptures depicting virgin martyrs by various sculptors for the church of Santa Maria di Loreto in front of the Roman Forum of Trajan (1630–33).

Duquesnoy was about to sail from Livorno, when he died; he had suffered for years from gout and episodes of vertigo (he fell from the scaffolding while attaching the gilded palm branch to his Susanna) and bouts of depression.

[5] Like other sculptors working in 17th century Rome, Duquesnoy was called upon to restore and complete antiquities, for headless torsos rarely found a market with contemporary connoisseurs.

With the Rondanini Faun (1625–30; now in the British Museum) Duquesnoy amplified a torso into a characteristically Baroque expansive gesture that deeply satisfied contemporary taste but was bitterly criticised by Neoclassicists by the end of the 18th century.

Giustiniani commissioned a life-size Virgin and Child from Duquesnoy in 1622, at a moment when the sculptor was hard pressed to finish his Andrew, due to interruption of payments instigated by a cabal (Joachim von Sandrart).