Wang Zhi was a native of She County of Huizhou (in present-day Huangshan City, Anhui). His mother was surnamed Wāng () as opposed to his father's Wáng () — owing to the similar surnames of his parents, some sources refer to Wang Zhi by his mother's surname, thus rendering his name as Wāng Zhi 汪直 instead of Wáng Zhi 王直. Wang Zhi became a salt merchant early in his life, following the mercantile tradition of Huizhou which had been rejuvenated by their ready access to the Ming government salt monopoly. However, despite amassing a sizable wealth from the salt trade, his business failed, and he was compelled to seek his fortune in the southern province of Guangdong with business associates Xu Weixue () and Ye Zongman () in 1540. Owing to the lax regulation on maritime trade in Guangdong, Wang Zhi and his associates were able to build great seaworthy junks, which they used to carry contraband goods such as saltpeter, silks, and cotton to the markets of Southeast Asia and Japan. During his time in Southeast Asia, he became acquainted with the Portuguese, who had been in the area since they captured Malacca in 1511.