As his farming family moved progressively westward from Wisconsin to Iowa and then to the Dakotas, Garland rebelled against the vicissitudes of pioneering and went to Boston for a career in 1884. Self-educated there, he gradually won a place for himself in the literary set of Boston and Cambridge and was influenced by the novelist William Dean Howells. Garland recorded the physical oppression and economic frustrations of pioneer life on the Great Plains in the short stories that were collected in Main-Travelled Roads (1891), one of his best works. The short stories he published in Prairie Folk (1892) and Wayside Courtships (1897) were later combined in Other Main-Travelled Roads (1910). In 1892 Garland published three lacklustre novels. His next novel, Rose of Dutcher's Coolly (1895), tells the story of a sensitive young woman who rebels against the drudgery of farm life and goes to Chicago to pursue her talent for literature. Garland's critical theory of “veritism,” set forth in the essay collection Crumbling Idols (1894), called for the use of socially conscious realism combined with more individualistic and subjective elements.

Garland next turned to the “high country” of the American West and to romantic melodrama for materials, producing a series of mediocre novels that were serialized in the popular “slick magazines.” He grew increasingly critical of the “excesses” of the naturalists, and in 1917 in a mellow autobiographical mood wrote A Son of the Middle Border, in which he described his family background and childhood as the son of pioneer farmers. This book won immediate and deserved acclaim. Its sequel, A Daughter of the Middle Border (1921), was less successful, as were Trail-Makers of the Middle Border (1926) and his last historical and autobiographical novels.