The Last Supper (da Vinci, 1498)

The Last Supper covers a 460cm x 880cm wall in Milan's Convent of Santa Maria delle Grazie, a UNESCO World Heritage Site, and has undergone 20 major restorations—more than any other artwork on this list. Painted by Leonardo da Vinci between 1494 and 1498, its experimental tempera-and-oil technique on dry plaster caused rapid deterioration, unlike traditional frescoes. While the Mona Lisa draws more annual visitors, The Last Supper has been copied more times than any other painting in history, appearing in over 1,000 known replicas and parodies. Its iconic depiction of Christ's final meal revolutionized narrative composition.