Half Cherokee, half Irish Johnny Devaney leaves Fort Gibson in the Indian Nations. The place is nothing more than a pest hole of disease and he hates that he has descended into living life as a filthy drunkard. He yearns for the woodlands and peaceful life he knew back in Tennessee and so he follows the rivers away from the fort into the Ozark country he recalls from the march through on the Trail of Tears.

Widowed pioneer settler Sabetha Trahern struggles to eke out her existence from the rough and rocky Ozark hills. One day as she struggles to bring her single cow home, she meets a stranger who drives the cow back to her crude barn but then collapses, ill.

She nurses Johnny Devaney, growing attached to him as he fights for his life against the deadly typhus fever he brought with him from Fort Gibson.

The title, The Marriage Cure, is taken from an old Irish proverb that says the only cure for love is marriage.