During the Depression's early years Lange's interest in social issues grew and she began to photograph the the effects of the economy on residents of the city.

A 1934 exhibition of these photographs introduced her to Paul Taylor, an associate professor of economics at the University of California at Berkeley, and in February, 1935 the couple together documented migrant farm workers in Nipomo and the Imperial Valley for the California State Emergency Relief Administration. Copies of the reports Lange and Taylor produced reached Roy Stryker, who headed the Resettlement Administration and offered Lange a job in August, 1935. Unlike the agency's other photographers, Lange did not move to Washington but used her Berkeley home as a base of operations. She and Paul Taylor were married that winter.

Lange returned to the Imperial Valley in early 1937 for the Resettlement Administration. The valley was in a state of crisis, and on February 16, 1937 Lange reported on the situation to Stryker:

“I was forced to switch from Nipomo to the Imperial Valley because of the conditions there. They have always been notoriously bad, as you know, and what goes on in the Imperial is beyond belief. The Imperial Valley has a social structure all its own and partly because of its isolation in the state, those in control get away with it. But, this year's freeze practically wiped out the crop and what it didn't kill is delayed – in the meanwhile, because of the warm, no rain climate and possibilities for work the region is swamped with homeless moving families. The relief association offices are open day and night 24 hours. The people continue to pour in and there is no way to stop them and no work when they get there.”

As many as 6,000 migrants arrived in California from the Midwest every month, driven by unemployment, drought, and the loss of farms.. In An American Exodus, which Paul Taylor co-authored with Lange, he wrote that the Okies and Arkies had "been scattered like the shavings from a clean-cutting plane." Many drifted to the Imperial Valley after the completion of Boulder (Hoover) Dam in 1936, which guaranteed the valley a supply of water for irrigation. This put further pressure on the migrants, who were already competing with Mexicans and other immigrants for work.

In October, 1936 due to shortages funds forced Stryker to lay off the photographers; however, after just two months, he was able to rehire Lange in late January, 1937. The several hundred photographs she took that year document the terrible conditions in California at the time, including makeshift camps on the banks of irrigation ditches, use of irrigation water for cooking and washing, crowds at the relief offices, and, when work was available, the stooped labor of working in the fields.