Gaine first entered into business as a printer and bookseller in New York city in 1750, and on August 3, 1752 established the
New York Mercury, a weekly newspaper. In 1767, Gaine modified the name and added
Gazette to his newspaper, now referred to as ''Gaine's New York Gazette and Mercury'' from that point on. He also functioned as a pressman, compositor, folder, and distributor of his own newspaper, which had a circulation of upwards to four hundred copies. When the
Stamp Act of 1765, with its proposed taxation of newspapers, legal documents and the like, was about to become law, Gaine, like many other American printers, suspended the publication of his newspaper in protest. For his printing of both patriot and loyalist articles, the
Sons of Liberty stormed Gaine's printing shop and threatened to destroy it in November 1775, which Gaine resented as his editorship was of a neutral nature in regards to American independence. They had advertised that their printing shop "has been open to publication from ALL PARTIES". When the Revolutionary war ended Gaine submitted a petition to remain in New York City, which was granted, but soon after he was compelled to hand over the publication of his failed newspaper, and confine his business ventures to private printing and bookselling, which he did do well at. ==Final years and legacy==