He was born in Florence, and carried a pike in the Spanish service at the age of sixteen. Two years later, on the outbreak of the Thirty Years' War in Bohemia, he was appointed a captain in a cavalry regiment sent by the grand duke of Tuscany to the emperor's army, and he fought with some distinction under Bucquoy at the battle of White Mountain in 1620 and in Hungary.
In 1624 he served for a short time in the Spanish army and then as lieutenant-colonel of Pappenheim's cuirassier regiment in the war in the Milanese. In 1627 he re-entered the Imperial service as colonel and captain of the lifeguard of Albrecht von Wallenstein, duke of Friedland. In this capacity he soon fell into disgrace for practicing extortion at Stargard in Pomerania, but his adroitness secured him, after no long interval, the rank of "colonel of horse and foot."
Ottavio Piccolomini was one of the closest associates of the Imperial general Wallenstein during the war. But after the appearance of Grantville, Wallenstein was defeated at the Battle of Alte Veste. When Wallenstein learned that Piccolomini was one of the men who assassinated him in another universe, Piccolomini quickly fled to Vienna.
In the year 1636, he was hired by Duke Maximillian of Bavaria to fight against Mike Stearns. He lead the Bavarian troops in the Battle of Moosburg.