Goodyear began his career as a partner in his father's hardware business, which went bankrupt in 1830. He then became interested in discovering a method of treating india rubber so that it would lose its adhesiveness and susceptibility to extremes of heat and cold. He developed a nitric acid treatment and in 1837 contracted for the manufacture by this process of mailbags for the U.S. government, but the rubber fabric proved useless at high temperatures.

For the next few years he worked with Nathaniel M. Hayward (1808–65), a former employee of a rubber factory in Roxbury, Mass., who had discovered that rubber treated with sulfur was not sticky. Goodyear bought Hayward's process. In 1839 he accidentally dropped some India rubber mixed with sulfur on a hot stove and so discovered vulcanization. He was granted his first patent in 1844 but had to fight numerous infringements in court; the decisive victory did not come until 1852. That year he went to England, where articles made under his patents had been displayed at the International Exhibition of 1851; while there he unsuccessfully attempted to establish factories. He also lost his patent rights there and in France because of technical and legal problems. In France a company that manufactured vulcanized rubber by his process failed, and in December 1855 Goodyear was imprisoned for debt in Paris. Meanwhile, in the United States, his patents continued to be infringed upon. Although his invention made millions for others, at his death he left debts of some $200,000. He wrote an account of his discovery entitled Gum-Elastic and Its Varieties (2 vol.; 1853–55).