Willa Cather based "Death Comes for the Archbishop" on William Howlett’s account of the life of Father Macheboeuf, vicar to Archbishop Lamy of New Mexico. Set in the mid-nineteenth century, the book follows the fortunes of Father Latour and his assistant and friend, Father Vaillant, as they organize the disjointed religious structure of the southwestern missions. The two face a formidable task, made more difficult by powerful priests long in control of the area who are loathe to abandon the corruption into which they have fallen. Working together diligently and with an unshakable faith, Father Latour and Father Vaillant eventually reclaim the region and bring its far-flung communities under the guidance of a single diocese.

First published in 1927, "Death Comes for the Archbishop" is the book that Cather believed to be her finest work. Like "The Professor’s House," it is a novel that explores the life of a man and draws on the American Southwest for its setting. Here the similarity ends, however, as the tone of the two books is quite different.

Unlike the earlier books, this one celebrates the life choices of its central characters, finding in the lives of Father Joseph Vaillant and Father Jean Marie Latour a simple dignity and extraordinary fulfillment.