At the age of fifteen, he worked on the whaleship Emily Morgan and had a red star tattooed on either his hand or his forearm (various versions as to the exact location of the marking have been reported).

[3] He and his brother, Charles, opened a dry goods store in Marysville, California, shortly after the city was founded at the height of the Gold Rush in 1850.

As the business grew, Macy's expanded into neighboring buildings, opening up more and more departments, and used publicity devices such as a store Santa Claus, themed exhibits, and illuminated window displays to draw in customers.

In 1875, Macy took on two partners, Robert M. Valentine (1850–1879), a nephew; and Abiel T. La Forge (1842–1878) of Wisconsin, who was the husband of cousin Margaret Getchell.

His will was probated on May 1, 1877, and he left his wife, Louisa H. "absolutely, all the paraphernalia, wearing apparel, watches, rings, trinkets, jewels, and personal ornaments reputed to belong to her, and during her life, the use of all the household furniture, books, clocks, bronzes, and works of art."