Apprenticed to a blacksmith at age 17, Deere set up his own smithy trade four years later and, for 12 years, did work in various towns of his native Vermont. In 1837, when 33 years old, he headed west and eventually settled in Grand Detour, Ill., where he set up a blacksmith's shop, and sent for his wife and children the following year. He joined in a partnership with Major Leonard Andrus.

In his work, Deere found, through the frequent repairs that he had to make, that the wood and cast-iron plow, used in the eastern United States from the 1820s, was not suited to the heavy, sticky soils of the prairies. He began experimenting, and by 1838 he and his partner had sold three newly fashioned plows. He kept experimenting, producing 10 improved plows in 1839 and 40 new plows in 1840. By 1846 the annual output was about a thousand plows. Deciding that Grand Detour was not well situated in regard to transportation and resources, Deere sold his interest in the shop to Andrus in 1847 and moved to Moline, Ill. There he began using imported English steel with great success and soon negotiated with Pittsburgh manufacturers for the development of comparable steel plate. By 1857 Deere's annual output of plows had risen to 10,000.

In 1858 Deere took his son Charles into partnership and in 1863 his son-in-law, Stephen H. Velie; in 1868 the firm was incorporated as Deere & Company (Deere & Company). Deere remained president of the company for the rest of his life. Gradually Deere & Company began manufacturing cultivators and other agricultural implements.