Frank emigrated to the United States in 1947 and worked as a photographer for the fashion and advertising industries in New York, before leaving everything behind to travel extensively in South America and Europe. In 1955 he was awarded a Guggenheim Fellowship to drive through the United States, with his family in tow, photographing the people, places and objects that he encountered.

Out of 28,000 frames, he selected 83 for his book The Americans published in the United States in 1959 with an introduction by Jack Kerouac, author of the cult novel On the Road. The deliberately grainy quality, apparently casual compositions and highly personal, observational style of these photographs have established The Americans as perhaps the most influential photography book of the last 50 years. In the late 1950s, Frank turned his attention to cinema. His films include Pull My Daisy 1959, which he made with his friends the Beat poets, and a documentary portrait of the Rolling Stones.