Cities of the Plain is the story of Billy and John Grady, two cowboys working in El Paso in the 1950s. Drought and famine have reduced the profitability of ranches, and the government threatens to exercise eminent domain and seize the ranch where the two men work. Their profitless existence only grows worse when Grady's lover, an epileptic woman named Magdalena, is murdered by her pimp. Grady and the pimp themselves fight to the death and Billy is left alone, drifting into homelessness but eventually reconstructing his life.
The story opens in 1952. John Grady Cole (the protagonist of All the Pretty Horses ) and Billy Parham (the protagonist of The Crossing ) work together on a cattle ranch south of Alamogordo, New Mexico, not far from the border cities of El Paso, Texas, and Ciudad Juárez in the state of Chihuahua, Mexico. The ranch's owners are kind but face an uncertain future in a dying industry. Recently devastated by drought, cattle ranches around El Paso are struggling and may be claimed by the Department of Defense, through eminent domain, to become military areas. Though the Cowboys barely make a living, John Grady and Billy love life on the open range, and John Grady – as detailed in All the Pretty Horses – is a master at training horses. Billy is an excellent tracker.
During a visit to a brothel in Juárez, John Grady falls in love with a young, epileptic prostitute, Magdalena. The couple plans to marry and live in the U.S., and John Grady renovates an abandoned cabin, turning it into a home. But Magdalena's brothel is run by Eduardo, a formidable adversary also in love with the young girl. Billy attempts to dissuade John Grady but feels obligated to help the couple.
Eduardo's sidekick, Tiburcio, murders Magdalena by cutting her throat, after she steals away from the brothel to meet John Grady at a crossing of the Rio Grande and leave Mexico. After John Grady finds her body in the morgue, he faces Eduardo in a knife fight reminiscent of his prison showdown in All the Pretty Horses . Though John Grady kills Eduardo, he is mortally wounded in the fight. He survives long enough to contact Billy, who hurries to comfort John Grady before his death.
After John Grady's death, a short epilogue—not unlike the conclusion of Blood Meridian (1985)—details, in a few pages, the next several decades of Billy's life. After drifting across the Southwest for many years, working ranches and living in hotels, Billy, homeless, takes shelter beneath a highway underpass. There, he meets a mysterious man who tells him about a convoluted dream. Thoughthe man denies it, Billy suspects he is Death. However, Billy survives the meeting with the man and finds shelter and a new life with a family who takes him in.