Kansas, 1910. Widowed farmer Jacob Witting finds that taking care of both his farm and two children, Anna and Caleb, is too difficult to handle alone. John takes out an ad in a newspaper for a mail-order bride, to which the "plain and tall" Sarah Wheaton answers, soon traveling from Maine to Kansas to become John's wife. Despite the love that grows between Sarah and the family, Sarah finds herself homesick, and she must ultimately choose whether or not to stay.

The Prairie is set at the time of the Louisiana Purchase. Hoping to find their destiny in the new territory, the Bush Family heads southward in a covered wagon. Sharing the family's numerous dangers and hardships are Ellen Wade (Lenore Aubert), sole survivor of an Indian attack, and army mapmaker Paul Hover (Alan Baxter). Cousins Abiram (Russ Vincent) and Asa (Jack Mitchum) duke it out over Ellen's affections

Jacob's farm is in trouble from a severe drought. Jacob and Sarah begin to wonder if Sarah can stay, and what will happen to Jacob if she and the children have to leave the farm.