Protestant artists fled France during the Wars of Religion for the same destinations, and at the same dates, as their coreligionists. Two waves of exile can be identified, the first during the sixteenth century, and the second during the seventeenth.

Despite early departures for Strasbourg and Geneva, the Huguenots left France in massive numbers only during the Wars of Religion proper (1562-1598). Some went to the provinces, such as Jacques I Androuet du Cerceau, who withdrew to Montargis in 1562. More often, they went abroad. This was the case for Jean Goujon, who took refuge in Bologna in 1562 or 1563, Bernard Palissy, who left for Sedan after the Bartholomew's Day Massacre (1572), and Barthélemy Prieur, who went to the same city after the enactment of the Edict of Nemours (1585).

It is not simple to determine the geography of this first Refuge. Although Goujon's departure for staunchly Catholic Bologna­­—where he would have a brush with the Inquisition—seems to have been motivated by artistic reasons, the choice of destination was soon dictated by religious criteria (channels were organized towards Protestant lands such as England, the Netherlands, and Geneva), proximity (the Principality of Sedan during the 1560s and 1570s, Geneva for the Lyonnais), and by the opportunities offered by lands of emigration (in 1550, Edward IV of England announced an edict favourable to Protestant immigration). Some of these lands imposed rules that were stricter than others. We know that Bernard Palissy had disagreements with the Église dressée (endowed with a pastor and a meeting space) at Sedan, and that the Council of Geneva did not allow the Parisian engraver Pierre Eskrich, called Cruche, to settle in the city in 1578, even though he had lived there off and on and had worked there since 1548.

For the Protestant artists of the sixteenth century who chose to put their art at the service of their religion, the return to France was difficult, if not impossible. Some left to contribute to the publication of Protestant Bibles or to disseminate the image of major reformers, such as the Lyonnais printer Jean II de Tournes. In 1580, he published the Icons of Theodore de Beze in Geneva, illustrated with portraits of reformers from woodcuts attributed to Pierre Eskrich. With respect to architects, some of them ensured the security of their coreligionists. Nicolas Bogueret from Langres, who took refuge in Geneva in 1570, put himself at the service of the Republic by supporting it at a time when "cities of religion" were being imagined and sometimes built in France. Exile, however, was not systematic for those who discreetly practiced their religion, since those in power often helped "their" artists. In 1552, Palissy was freed after the Connétable de Montmorency interceded on his behalf and secured for him Catherine de Medici's protection, which he apparently enjoyed during the Saint Bartholomew's Day Massacre. In 1575, after the death of Renée de France whom he had joined in Montargis, the architect Jacques I Androuet du Cerceau passed under the protection of Anna d'Este, the widow of the Duc de Guise and wife of the Duc de Nemours, who was herself actively involved in the Catholic League. Religious exile was hence not systematic, nor was it lasting, for many artists returned to France, for better or for worse: Palissy died in the Bastille in 1590; the more prudent Barthélemy Prieur, who in 1585, abandoned Paris and his position as Henri III's "sculpteur ordinaire," did not return to Paris until 1594, after Henri IV's coronation.

Proclaimed in 1598, the Edict of Nantes allowed Protestant artists to once again become loyal subjects of the patron king, who employed them at Fontainebleau, the Louvre, and the Tuileries. During the seventeenth century, the Du Cerceaux, Salomon de Brosse, Jacques Boyceau, Henri and Louis Testelin, along with Sébastien Bourdon and Abraham Bosse were employed by the king and his circle, to the point that the Charenton temple served as an "annex of the court" (Menna Prestwich). In 1648, the Protestants actively participated in the founding of the Académie. Nevertheless, the Calvinist position regarding religious images that Charles Drelincourt, the pastor of Charenton from 1620 to 1669, endeavoured to emphasize with his community, should have compromised the careers of the artists who had stayed in France, or at least prevented them from responding to religious commissions. Yet this was not true. One of the most emblematic cases of this golden age was that of the Calvinist Sébastien Bourdon. His career enables us to put into perspective the internal exile of Protestants, which is to say the modifications they had to make to their art in order to honour commissions from Catholic patrons, including religious ones. After a long stay in Italy, during which he was at risk of being denounced to the Roman Inquisition, Bourdon returned to Paris, where in 1642 he was notably tasked with producing the May, a painting that the goldsmith guild offered every year at Notre Dame. On various occasions he had to paint the Virgin, saints, and even the Trinity. In certain respects, France even represented a welcoming land for Protestant artists. In fact, many Flemish painters went to the "little Geneva" that was the Saint-Germain neighbourhood during the first half of the seventeenth century, and notably contributed to the success of "silent lives" (still lifes).

The respite lasted until the 1660s, at which time violence continued to increase until the revocation of the Edict of Nantes (1685). In 1667, the bylaws of silk workers in Lyon stipulated that "no-one could be admitted as a Master without being a Catholic," and in 1680, the Paris Parliament forbade the Reformed from practicing the goldsmith trade. Finally, on October 10, 1681, a text by Colbert addressed to Le Brun, the Director of the Académie at the time, definitively put an end to tolerance: "The King having been informed that the Misters Tetelin, Secretary of the Académie for Painting and Sculpture; Michelin, adjunct professor; Ferdinand, Bernard, and Rousseau, Counselors of the Académie; Lespagnandell and Ferdinand, members of the Académie, are all members of the supposed reformed religion, His Majesty has ordered me to notify M. Le Brun that he wants them to be stripped of their functions, and to have the Académie elect others in their place who are Catholics." Some renounced their faith, while others went into exile. Nicolas Eudes, Jacques d'Agard, and Jacques Rousseau left for London, Louis Testelin for The Hague, while Jean Michelin ended his days in Jersey.

It is impossible to say how many of the 200,000-250,000 Protestant who fled France at the time were artists. As in the sixteenth century, England, Saxony, Prussia, Holland, Ireland, and Geneva were the major destinations. In 1685, the Great Elector invited the exiled to go to Prussia, where they would embellish Berlin and Potsdam, while Peter the Great sought to attract them to Saint Petersburg in 1689. This exile of French talent towards the cities and courts of neighbouring countries contributed greatly to the "Frenchification of Europe" described by Louis Réau: a former member of the Académie, the portraitist Jacques d'Agard was named the first painter of the kings of Denmark and Norway; a fine connoisseur of French palaces and hotels particuliers, Daniel Marot was chosen by William III of Orange to adorn the Het Loo Palace; tasked in 1685 with erecting Christian V's equestrian statue in the royal plaza of Copenhagen, the French sculptor Abraham-César Lamoureux took inspiration from the Louis XIV on horseback that Girardon created at the time for Louis-le-Grand plaza (today's place Vendôme).

Unlike the departures of the sixteenth century, none returned from the Great Refuge.