As a young man O'Neill left Ireland (likely in 1607 during the Flight of the Earls). He grew up in the Spanish Netherlands and served for 40 years in the Irish regiment of the Spanish army. Most of his combat was in the Eighty Years' War against the Dutch Republic in Flanders and against the French in the Franco-Spanish War. He distinguished himself notably at the Siege of Arras in 1640, where he commanded the Spanish garrison and held out for 48 days with 2,000 men (many of whom were fellow Irishmen), against a French army of 35,000. Throughout his career O'Neill was known to be an expert in defensive warfare.