After the Portuguese gained permission from the Ming mandarins to establish a permanent settlement and trade base in Macau in 1557, the port of Macau benefited greatly from being the intermediary of the lucrative China–Japan trade, since the direct routes were banned by the Ming court due to fears of the wokou pirates. Portugal's success in Macau drew the envy of other European maritime powers who were slower to gain a foothold in East Asia. When Philip II of Spain became King of Portugal after the 1580 Portuguese succession crisis, Portuguese colonies came under attack from Spain's enemies, especially the Dutch and the English, who were also hoping to expand their overseas empires at the expense of a country that had largely ceased to exist.
Macau had been raided by the Dutch in 1601, 1603, and 1607, but the Dutch invasion of 1622 represented the first real attempt to capture the city. The Hollanders, frustrated that their trading post at Hirado was unable to compete with the Portuguese traders at Nagasaki as a result of the latter's easy access to China, hoped that the capture of Macau would grant them a commercial base in China while at the same time depriving the Portuguese of the profitable Macau–Nagasaki route. The fall of Macau would also leave the Spaniards in the Philippines without means of support and make it easier for the Dutch to mount an attack on Manila.
Despite the raids, the Portuguese authorities had not raised an extensive defensive system for the city, because of interference by Chinese officials. Macau defense in 1622 consisted of a few batteries, one at the west end of the Macau Peninsula (later site of the São Thiago da Barra fortress), and one at each end of the southern bay of Praia Grande (São Francisco on the east and Bom Parto on the west), plus a half-completed Fortaleza do Monte that overlooked the Cathedral of St. Paul.
The sorry state of Macau's defenses became known to the Hollanders when the Dutch ship Gallias seized a Portuguese ship carrying a case of letters off the coast of Malaya at the end of 1621. Judging by these intercepted letters and information available from Japan, the Governor-General of the Dutch East Indies Jan Pieterszoon Coen considered that Macau was not in a position to resist a serious attack, and set his invasion plan in motion.