Eastern harvest mice are omnivores, feeding on seeds, insects, and green vegetation. Seeds of grasses, sedges, and forbs make up a major part of the diet. Insects including grasshoppers, beetles, caterpillars, ants, and wasps are also consumed. Green leaves, shoots, and stems provide moisture.
Eastern harvest mice will climb into low shrubs and vines up to 2 meters high to reach seeds, fruits, and insects. But most foraging occurs on the ground among dense grasses and herbaceous plants. Food caches may be created in nests. The mice do not hibernate but remain active year-round.