Texas Governor Elisha Pease sends a small troop of Texas Rangers, under the leadership of Captain Inish Scull, to the Llano Estacado in pursuit of the celebrated Comanche horse thief, Kicking Wolf. This bold Indian steals Hector, Scull's famous horse, and takes it to the Sierra Perdida to give to the notorious Mexican bandit Ahumado, feared for the horrible tortures that he inflicts upon his victims. Scull, promoting McCrae and Call to Captains and instructing them to lead the Ranger troop back to Austin, sets off on foot after Kicking Wolf, accompanied only by the Kickapoo tracker Famous Shoes. Ahumado ties Kicking Wolf up to be dragged away by a horse, and takes Kicking Wolf's companion, Three Birds, prisoner. Ahumado intends to impose a slow death on Three Birds, but Three Birds throws himself off a cliff. Scull finds the unconscious Kicking Wolf being dragged by the horse, and cuts the Comanche's bonds, which allows Kicking Wolf to survive and return to his tribe. Scull is soon captured by Ahumado, and placed in a cage, where he is supposed to die slowly.
Having returned to Austin, McCrae learns that his beloved Clara Forsythe intends to marry his rival, horse trader Bob Allen (though she is not married yet, as Scull's wife had led McCrae to believe). Call learns that his lover, the reluctant whore Maggie Tilton, is pregnant with his child. Prompted by Scull's insistent and promiscuous wife Inez, Governor Pease sends Call and McCrae out in charge of another typically small Ranger troop to rescue Captain Scull. While they are on this mission, Comanche chief Buffalo Hump leads his nation on the warpath. They burn much of Austin, killing Clara's parents and ravaging fellow Ranger Long Bill Coleman's wife, Pearl. Maggie, having been prepared by Call, hides under a smokehouse, thus escaping the Comanches' notice.
The Rangers turn back to Austin as soon as they hear of the raid there. Pearl and Long Bill are unable to recover emotionally, and Long Bill hangs himself.
Scull handles the cage so well that Ahumado has him taken down, and has his henchman Goyeto cut off his eyelids. Ahumado sends word to Austin that he will return Scull for a ransom of one thousand cattle. Governor Pease sends the Rangers out once again, to collect the cattle and exchange the herd for Scull. The Rangers go to Lonesome Dove in search of cattleman Captain King. Realizing they will not be able to even gather the cattle, let alone persuade King to sell them, Call and McCrae set out to try to rescue Scull on their own terms, leaving the rest of their troop behind. Meanwhile, Ahumado has been bitten by a brown recluse spider, and goes South to die. Call and McCrae find Scull going insane in a pit, but the rescue is soon enough to allow Scull to mostly recover. Scull returns to Austin and later becomes a general with the Union army. Because of the eyepieces he has devised, he becomes known as "Blinders" Scull.
Meanwhile, Buffalo Hump banishes his half-Mexican son Blue Duck. Blue Duck goes East and acquires wealth and notoriety as the leader of a gang of bandits.
At this point, the novel moves more quickly, giving highlights covering the period leading up to the sequel, Lonesome Dove . Maggie gives birth to Call's son Newt, but Call refuses to acknowledge the child is his. She goes to work at the general store, and Jake Spoon more or less moves in with her. The Civil War takes most of the soldiers away from the frontier, enabling the Comanches to push back the white settlers. After the Civil War, Call and McCrae are sent in pursuit of Blue Duck and his band of renegades. Buffalo Hump has gone off to die. Blue Duck hears of this and leaves his cutthroats to pursue his father. The Rangers attack his band, but Blue Duck, having left, evades capture. He finds his father at his chosen place of death and kills him there. Maggie dies while the Rangers are on this expedition.