There are three main settings in Water for Elephants. First, young Jacob is found on the campus of Cornell University in Ithaca, New York. His stay here is cut short by the death of his parents. Another setting is the interior of a nursing home, where ninety-year-old Jacob has been placed after the death of his wife. His children are all grown and are not willing to share their lives with Jacob.

The majority of the story, however, takes place in the traveling circus, where the setting is either on a moving train or under the big circus tents. The train takes the circus all over the United States, usually stopping only for a day or two. There are hints of the effect of the Great Depression on people in the cities the circus visits, thus expanding the setting to capture the history around the characters.