The Italian War of 1542–1546 was a conflict late in the Italian Wars, pitting Francis I of France and Suleiman I of the Ottoman Empire against the Holy Roman Emperor Charles V and Henry VIII of England. The course of the war saw extensive fighting in Italy, France, and the Low Countries, as well as attempted invasions of Spain and England. The conflict was inconclusive and ruinously expensive for the major participants.

The Italian Wars were a series of conflicts fought between 1494 and 1559, mostly in the Italian Peninsula, but later expanding into Flanders, the Rhineland and Mediterranean Sea. The primary belligerents were the Valois kings of France, and their Habsburg opponents in the Holy Roman Empire and Spain. At different points, various Italian states participated in the war, some on both sides, with limited involvement from England and the Ottoman Empire.