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Set in the late 19th century, the story focuses on the forbidden romance between the title character and Johnse Hatfield, whose families have been feuding for many years. The two meet when she is stung by a hornet while picking flowers for a picnic table at the local fair and he comes to her aid. When she discovers his identity, she angrily accuses his clan of having shot and injured her mother in the distant past. Johnse protests that Mounts, who was responsible for the accident, was innocent by reason of insanity, but Roseanna wants no part of him.
Later that evening, Johnse takes Roseanna aside and kisses her, unaware they are being observed by her brother Little Randall. She is enchanted by his advances and, when shopkeeper Thad Wilkins proposes marriage to her several days later, she rejects him. Johnse takes her from her home in Kentucky across the Big Sandy River to his home in West Virginia, where he introduces her to his parents, Devil Anse and Levisa, as his future bride.
Anse uses the engagement as a reason to renew hostilities with the McCoys, and he and his sons Ellison and Cap prepare for battle. While Johnse seeks a preacher to perform the wedding ceremony, Roseanna and Levisa begin to bond. Cap is injured in an accident, and while his parents tend to his wounds, the psychotic Mounts arrives at the Hatfield cabin and threatens Roseanna, who is rescued by Anse.
While fetching water, Roseanna is approached by Little Randall, and she agrees to return home. She bids Johnse farewell and asks him to call on her father Old Randall the following evening. While en route to the McCoys, Johnse stops at Thad's store and meets Tolbert, Phamer, and Little Randall McCoy. Mounts enters and starts a brawl, and the melee escalates into a gunfight.
Thad carries the wounded Tolbert to the McCoy house, where Roseanna and her father are awaiting Johnse's arrival, and reports Little Randall is injured and trapped in the store with the Hatfields. After ordering his relatives to hold their fire, Johnse admits Roseanna, Old Randall, and Thad to the store. Mounts uses Roseanna, Johnse, and Little Randall as shields to escape, and Old Randall declares war against the Hatfields.
During the fighting, Johnse and Roseanna secretly meet, and Johnse shoots and injures Mounts before he can shoot them. As they flee on horseback, Mounts takes aim at them and is killed by Anse. The two clans lay down their weapons and watch Johnse and Roseanna ride off in search of a preacher and future happiness.