After his education in the public schools of Rochester, New York, Eastman worked briefly for an insurance company and a bank. In 1880 he perfected a process of making dry plates (dry plate) for photography and organized the Eastman Dry Plate and Film Company for their manufacture. The first Kodak (a name he coined) camera was placed on the market in 1888. It was a simple, hand-held box camera containing a 100-exposure roll of film that used paper negatives. Consumers sent the entire camera back to the manufacturer for developing, printing, and reloading when the film was used up: the company's slogan was “You press the button, we do the rest.” In 1889 Eastman introduced roll film on a transparent base, which has remained the standard for film. In 1892 he reorganized the business as the Eastman Kodak Company. Eight years later he introduced the Brownie camera, which was intended for use by children and sold for one dollar. By 1927 Eastman Kodak had a virtual monopoly of the photographic industry in the United States, and it has continued to be one of the largest American companies in its field.

Eastman gave away half his fortune in 1924. His gifts, which totaled more than $75,000,000, went to such beneficiaries as the University of Rochester (of which the Eastman School of Music is a part) and the Massachusetts Institute of Technology in Boston. He was also one of the first owners to introduce profit sharing as an employee incentive. Eastman took his own life at age 77, leaving a note that said, “My work is done. Why wait?” His home in Rochester, now known as George Eastman House, has become a renowned archive and museum of international photography as well as a popular tourist site.