The Truce of Nice, which had ended the Italian War of 1536–38, has provided little resolution to the long conflict between the Holy Roman Emperor and the King of France; although hostilities had ended, giving way to a cautious entente, neither monarch is satisfied with the war's outcome.

Francis continues to harbor a desire for the Duchy of Milan, to which he holds a dynastic claim; Charles, for his part, insists that Francis comply at last with the terms of the Treaty of Madrid, which had been forced on the French king during his captivity in Spain after the Italian War of 1521–1526.

Other conflicting claims to various territories—Charles's to Burgundy and Francis's to Naples and Flanders, among others—remain a matter of contention as well.

Negotiations between the two powers had continued through 1538 and into 1539.

In 1539, Francis had invited Charles—who was facing a rebellion in the Low Countries—to travel through France on his way north from Spain.

Charles had accepted, and been richly received; but while he was willing to discuss religious matters with his host, he delayed on the question of political differences, and nothing had been decided by the time he left French territory.

In March 1540, Charles had proposed to settle the matter by having Maria of Spain marry Francis's younger son, the Duke of Orléans; the two would then inherit the Netherlands, Burgundy, and Charolais after the Emperor's death.

Francis, meanwhile, was to renounce his claims to the duchies of Milan and Savoy, ratify the treaties of Madrid and Cambrai, and join an alliance with Charles.

Francis, considering the loss of Milan too large a price to pay for future possession of the Netherlands and unwilling to ratify the treaties in any case, had made his own offer; on April 24, he had agreed to surrender the Milanese claim in exchange for immediate receipt of the Netherlands.

The negotiations have continued for weeks, but make no progress, and are abandoned in June 1540.

The French immediately launch a two-front offensive against Charles.

In the north, the Duke of Orléans attacks Luxembourg, briefly capturing the city; ...

...in the south, a larger army under Claude d'Annebault and Francis's eldest son, the Dauphin Henry, unsuccessfully besiege the city of Perpignan in northern Spain.

Francis himself is meanwhile in La Rochelle, dealing with a revolt caused by popular discontent with a proposed reform of the gabelle tax.

Two Imperial armies are massed to invade France by May 1544: one, under Ferrante Gonzaga—former condotiorro and, from 1535, Viceroy of Sicily—north of Luxembourg; the other, under Charles himself, in the Palatinate.

Gonzaga captures Luxembourg on May 25.

Moving towards Commercy and Ligny, he issues a proclamation that the Emperor has come to overthrow "a tyrant allied to the Turks.”

Gonzaga besieges Saint-Dizier on July 8; Charles and the second Imperial army soon join him.

Twenty-five year old René of Châlon, born in Breda as the only son of Count Henry III of Nassau-Breda and Claudia of Châlon, had inherited the Princedom of Orange in 1530 at the death of Claudia's brother, Philibert of Châlon, the last Prince of Orange from the house of Châlon, on condition that he use the name and coat of arms of the Châlon-Orange family.

History knows him therefore as René of Châlon instead of as "René of Nassau-Breda."

René of Châlon had married Anna of Lorraine (1522-1568) on August 20, 1540 at Bar-le-Duc.

They had only one child, a daughter named Maria, who lived only three weeks and was buried in the "Grote Kerk" in Breda.

René is mortally wounded in battle while taking part in the siege of St. Dizier, and dies on July 15 with the Emperor attending at his bedside.

René's eleven-year-old cousin William of Nassau-Dillenburg (better known as "William the Silent"), the eldest son of Count Willem the Rich of Nassau-Dillenburg, inherits all of René’s vast possessions, the combined wealth of the houses of Nassau-Breda in the Low Countries and of the Provençal principality of Orange.

William adds the name of Orange to his own paternal dignities and and thus becomes the founder of the House of Orange-Nassau.

Henry had meanwhile ordered Suffolk to attack Boulogne, crossing on July 14 to Calais and moving to join him.

The Siege of Boulogne begins on July 19—despite the protests of the Emperor, who insists that Henry should advance towards Paris.

Charles himself, on the other hand, is still delayed at Saint-Dizier; the city, fortified by Girolamo Marini and defended by Louis IV de Bueil, Count of Sancerre, continues to hold out against the massive Imperial army.

Charles captures Vitry, from which French forces have harassed his supply lines, on July 24; ...

...the defenders of Saint-Dizier, running low on supplies, finally seek terms on August 8.

The French capitulate on August 17 and are permitted by the Emperor to leave the city with banners flying; their resistance for forty-one days has broken the Imperial offensive.

Some of Charles's advisers suggest withdrawing, but ...

...he is unwilling to lose face and continues to move towards Châlons, although the Imperial army is prevented from advancing across the Marne by a French force waiting at Jâlons.

The Imperial troops march rapidly through Champagne, capturing Épernay, ...