He entered the Jesuit novitiate in 1602, and on 29 March 1608, he left for Goa and the Far East aboard Nossa Sra.

Semedo changed his Chinese name from Xie Wulu to Zeng Dezhao and re-entered China, now working in Jiangsu and Jiangnan provinces.

He spent most of his term in China in the central and southern provinces; perhaps his only trip north was the one he made to Xi'an in 1625, during which he was the first European to see the recently unearthed Nestorian Stele.

During several years after the fall of Beijing to the Manchus in 1644, he continued to work with the Ming loyalist regimes in the Southern China (notably, sending Michał Boym to the court of the Southern Ming Yongli Emperor),[2] even as most Jesuits elsewhere in China were switching their loyalty to the recently established Qing dynasty.

Once the Qing took Canton, Semedo was detained, but was freed a few months later, reportedly due to the interference of Beijing-based Johann Adam Schall von Bell.