January 5, 1500 – Duke Ludovico Sforza conquers Milan.

January 26, 1500 – Vicente Yáñez Pinzón becomes the first European to set foot on Brazil.

February 17, 1500 – Duke Friedrich and Duke Johann attempt to subdue the peasantry of Dithmarschen, Denmark, in the Battle of Hemmingstedt.

March 9, 1500 – The fleet of Pedro Alvares Cabral leaves Lisbon for the Indies. The fleet will discover Brazil which lies within boundaries granted to Portugal in the Treaty of Tordesillas.

March 29, 1500 – Cesare Borgia is given the title of Captain General and Gonfalonier by his father Rodrigo Borgia after returning from his conquests in the Romagna.

April 10, 1500 – Ludovico Sforza is captured by the Swiss troops at Novara and is handed over to the French.

April 22, 1500 – Portuguese navigator Pedro Álvares Cabral lands in Brazil.

November 11, 1500 – Treaty of Granada – Louis XII of France and Ferdinand II of Aragon agree to divide the Kingdom of Naples between them.

February 22, 1500 – Cardinal Rodolfo Pio da Carpi, Italian humanist (d. 1564)

February 24, 1500 – Charles V, Holy Roman Emperor (d. 1558)

April 12, 1500 – Joachim Camerarius, German classical scholar (d. 1574)

April 23, 1500 – Alexander Ales, Scottish theologian (d. 1565)

November 3, 1500 – Benvenuto Cellini, Italian artist (d. 1571)