In 1865, Cullen Bohannon, a former Confederate soldier, seeks to avenge his wife’s rape and murder by Union soldiers. His quest leads him to Hell on Wheels, the roving tent city that accompanies the transcontinental railroad’s western expansion. Back East, Thomas Durant, the Union Pacific Railroad’s boss, lines up investors and enriches himself by siphoning off government subsidies.
Reverend Nathaniel Cole converts a Cheyenne Indian named Joseph Black Moon to Christianity, and the two pitch Cole’s church tent in Hell on Wheels. Farther west, Cheyenne braves murder Robert Bell, the railroad’s chief surveyor. Lily, his wife, kills their attacker and escapes with Robert’s maps.
Daniel Johnson, the railroad’s foreman, hires Cullen to supervise an all-black “cut crew” preparing the terrain for track laying. Johnson subsequently admits to participating in the attack on Cullen’s wife with another railroad employee, later revealed as Sergeant Frank Harper. Elam Ferguson, the black crew’s leader, slits Johnson’s throat before he can kill Cullen.
The Swede, the Union Pacific’s security chief, accuses Cullen of Johnson’s murder and schedules a hanging. The Swede polices lawless Hell on Wheels but also shakes down its residents, among them Sean and Mickey McGinnes, two brothers who make money showing slides of Ireland to their homesick compatriots.
Cheyenne braves, including Joseph’s brother, Pawnee Killer, stalk the wounded Lily. Durant offers a bounty for her rescue, though he’s more concerned about Robert’s maps.
Cullen eludes The Swede and visits Durant in his plush Pullman car to request Johnson’s job. Cullen’s audacity impresses Durant and he hires him.
Joseph rescues Lily in the wilderness. Cullen, still pursuing Sergeant Harper, comes across them and escorts Lily to town.
Elam attempts to patronize a white prostitute named Eva, invoking the outrage of Mr. Toole, the Irish walking boss.
At a funeral for the massacre victims, Cole pleads for peace, but Durant urges the attendees not to let “Stone Age primitives” prevent the railroad’s progress.
Cullen tracks down Harper, who shoots Cullen’s horse and escapes. The Swede overhears Durant speculating on R&R Railroad stock using Union Pacific funds. Though staying in Durant’s Pullman, Lily doesn’t reveal that she has the maps.
Eva and Elam meet in secret and bond over their outcast status, he for being black and she for being enslaved and tattooed by Indians as a young girl.
The Swede bribes Cullen to ignore the theft of powder explosives. After the theft occurs, some of the explosive accidentally ignites, causing mass carnage. Cullen saves a man’s life, ignoring The Swede’s warning to evacuate.
Seeking a vision, Pawnee Killer begins a full-day ritual alone in the woods. With payroll late, Durant instructs Cullen to bribe the walking bosses to keep everyone working.
A U.S. Army advance party rides into town. Cole prepares to warn Chief Many Horses of the Cheyenne. Before Cole leaves, his long-lost daughter Ruth arrives unexpectedly.
Sean and Mickey fail to pay The Swede, so he chops down their tent. Out at the cut, Cullen and Elam scuffle over the late payroll. As a distraction, Durant proposes that they box for real. Sean bets heavily on Elam and fixes the fight so Elam wins, unaware of his own cheating. Outside, Lily informs Durant that she has Robert’s maps but doesn’t disclose where.
Pawnee Killer completes his ritual and describes a vision in which he kills the “great steel beast.”
Senator Crane arrives to negotiate with Chief Many Horses. The Swede informs Crane of Durant’s stock speculation and in return asks for information about Frank Harper.
Chief Many Horses refuses Crane’s offer of life on a reservation. After hearing the chief describe his son’s vision of defeating the train, Durant proposes that Pawnee Killer race on horseback against a locomotive, which wins. That night, Lily overhears Crane threaten to ruin Durant over the stock speculation and relinquishes the maps so that Durant can complete Robert’s vision of the transcontinental railroad.
Toole and his men catch Elam with Eva together and string him up for a hanging. Cullen rescues Elam, and the two flee town on horseback. While on the run, they share stories about their lives in the South. Cullen teaches Elam how to shoot a gun and count his opponent’s bullets.
En route to Chicago with Lily, Durant despairs that Crane will ruin him. Lily chides Durant for self-pity, after which he develops a plan to mollify Crane with a stock tip.
In Chicago, Durant tells Crane he’ll make a fortune if he buys R&R stock. Lily visits Robert’s family and receives a cold greeting from his sister, who blames Lily for Robert’s death. Lily recounts her ordeal to the room in gory detail as Durant watches.
A posse led by two of The Swede’s henchmen begins a shootout with Cullen and Elam. Toole maneuvers himself in front of Elam, who has counted bullets and realizes that Toole’s gun is empty. Elam shoots Toole in the mouth.
Durant makes millions by purchasing the M&M Railroad instead of the R&R and visits Crane to gloat over his financial ruin.
On the return trip to Hell on Wheels, Durant stuns Lily by courting her. Indians sabotage the tracks and derail the train ahead of Durant’s, killing and wounding many passengers.
Cullen, Elam, and Joseph join a response party led by Lieutenant Griggs of the U.S. Army. When a Union soldier is discovered hanging mutilated from a tree, Griggs blames the incident on Chief Many Horses, but Joseph insists that it’s the work of Pawnee Killer.
In despair over the train attack, Reverend Cole begins drinking again. Ruth accuses him of getting drunk and beating her mother. Ruth smacks her father and tells him that she isn’t afraid of him.
To assert her independence, Lily moves out of Durant’s Pullman and into a tent near the cathouse. Lily and Eva describe their experiences with Indians to each other.
The Swede tells Durant he can prove that Cullen is a killer, but Durant doesn’t care, calling Cullen an “an agent of progress.”
Cheyenne braves attack Griggs’ search party with arrows, guns and tomahawks and are met with gunfire. Joseph rescues Griggs, then chases and kills Pawnee Killer. With the Indians defeated, Elam slices a few scalps and claims the bounty from Durant. Impressed, Durant hints of future “tasks” for Elam.
Now flush with cash, Elam asks Eva “to be mine, none other.” Toole arrives at camp, miraculously still alive, and begs forgiveness from Eva and Elam.
Joseph performs a burial ritual for Pawnee Killer. Chief Many Horses acknowledges that Pawnee Killer needed to be stopped. “I killed my own brother,” Joseph later weeps to Ruth, who comforts him with a kiss that he returns.
The railroad crew meets the government deadline for laying 40 miles of track. Durant expresses his gratitude by alerting Cullen to The Swede’s summoning of Federal Marshals to arrest Cullen for murder.
Griggs tells Cole he intends to kill Joseph. Cole grabs Griggs’ saber and slices off Griggs’ head.
Durant asks Lily to assume her “fair-haired maiden of the West” persona to impress investors attending a dance to celebrate the track-laying milestone. After Durant promises a continuing role for Lily with the railroad, she plays her part convincingly.
Elam tells Eva he’s not ready for marriage but at the dance becomes outraged to find Toole dancing with her. Eva says that she and Toole have decided to stay behind and settle down together.
Meanwhile, Sean and Mickey incite the townsfolk to tar and feather The Swede. Cullen hunts down Harper and strangles him, only to realize that he was innocent. After briefly watching Lily with Durant at the dance, Cullen flees town on horseback. The next day The Swede comes across a poster offering a $250 bounty for Cullen’s capture.