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Jean-Guillaume Moitte was born in Paris to an artist father, Pierre-Etienne Moitte, who was an Academician and professional engraver. From 1761 to 1764 he trained under the sculptor Jean-Baptiste Pigalle and then transferred to the atelier of Jean-Baptiste Lemoyne, the favourite sculptor of King Louis XV. Despite this training and various important commissions, including the decoration for Parisian toll barrières built around Paris between 1785 and 1789 to raise revenue for the government, the period that most influenced Moitte's oeuvre was his time at the Académie in Rome. Here he studied Roman reliefs, vases, urns and sarcophagi, and it was this concentration on the art of antiquity that inspired him on his return to France.

In 1768 he won the Prix de Rome in sculpture for The Triumphant David Carrying the Head of Goliath and subsequently three years at the École Royale des Élèves Protégés. Moitte exhibited at the Salon in 1783, the same year he became an asoociate in the Académie. During the Revolution he was awarded a commission for a statue of Jean-Jacques Rousseau to be raised on the Champs-Élyssées. Near the end of his life he was commissioned by Napoleon to execute the tomb of Général Desaix in the chapel of the Grand-Saint-Bernard hospice in the Alps.