In this, the pilot episode, we are introduced to six Pony Express riders, their sage mentor and boss, Teaspoon, their station mother, Emma, and the local marshal, Sam, as well as the concept of the Pony Express itself. More specifically, The Kid earns his trusty horse, Katy, learns a little about the nature of good and evil, and becomes the first to discover Lou's secret.
When the Kiowa begin to attack white settlements and civilians, Buck must decide between loyalty to his Kiowa brother and to the obligations and friendships he has found with the Pony Express. In the meantime, Lou, Hickok and Cody get into a fight with Tompkins and his men because of the shopkeeper's insults against Buck.
While on an Express run, Ike witnesses a terrible stagecoach massacre and finds himself unable to take the life of the gang's leader. The man is apprehended, however, and it is up to the Riders to ensure Ike's safe passage to the courthouse where he can testify.
Lou ventures back to the orphanage where she grew up in order to see her younger brother and sister for the first time in five years. However her estranged father, a villainous gunrunner, has taken the children to his canyon fortress. Can Lou rescue her siblings and keep her secret from the other Riders?
When an escaped slave helps around Emma's farm and saves The Kid's horse, Katy, from a fire, the Riders must decide whether to obey the law - the Fugitive Slave Act - or act to save a man who has suffered a life of injustice and cruelty.
After Jimmy insults a dime novel author named Marcus, he suffers the consequences of much unwanted notoriety as the exaggerated subject of Marcus's newest novel. Guns blazing, hired hitmen and toughs arrive in Sweetwater, determined to take down Wild Bill Hickok, the fastest gun in the West.
The Kid's estranged brother Jed is up to no good. After bushwhacking an Army detachment and stealing their identities, Jed and his gang ingratiate themselves with the Riders while angling to receive a gold shipment intended for the US Government. When Sam becomes suspicious, The Kid must decide between family and justice.
The Kid discovers a half-Hunkpapa warrior, Curly, at the sight of an apparent Sioux massacre and takes him into custody. Curly's smart mouth does nothing to ease tensions in Sweetwater, but The Kid and the Riders come to trust him. Were the Sioux really responsible for the massacre or is someone trying to set up the tribe?
When Emma insists on traveling to Ft. Reunion to help deliver her friend's baby, Hickok accompanies her. They become virtual prisoners of an ambitious captain who schemes to incite an Indian war and make a name for himself on the frontier. Trapped, Emma and Jimmy must rely on each other for survival and comfort.
Hickok falls hard for a young woman named Sarah who, unbeknownst to him, is married. When her husband is shot dead, Jimmy is imprisoned and tried for murder. But what is it Sarah's deceptive nature and a lying cattle wrangler that feels all wrong? Sam and the Riders work together to solve the mystery before Jimmy hangs.
Hickok has a fight with Teaspoon and agrees to go to work in a brothel where the madam, Grace Rollins, has taken a fancy to Jimmy. But deceptions abound: Grace has her eye on a secret Army cache of weapons she plans to sell on the black market, and Jimmy has his eye on her illegal schemes.
Cody and The Kid, on special assignment, stop for refreshments in a little town called Prosperity. When The Kid tries to defend a woman and gets into trouble with local lawmen, Cody suspects that not all is right with the strange town. He seeks the Riders' aid to help rescue The Kid from terrible punishment.
While away from Sweetwater on a run, Lou impulsively buys a dress and tours a new town as the young woman she is. An insurance salesman, Tyler Dewitt, takes Lou out to dinner, and she becomes enamored of him. But is the polite salesman all he appears? And what will The Kid think?
Evan, Emma's estranged husband, returns, reminding Emma of her difficult past and driving a wedge between her and Sam. But despite any reluctant loyalty she feels for him, even Emma must admit that Evan's behavior is suspicious. Just what is his link to a terrible stagecoach massacre?
The Army requests a rider to deliver a special dispatch, and Cody volunteers for the job. Along the way, he encounters brigands, a bear, and a desolate widow, but he remains committed to his task. Meanwhile, the Riders tend to an abandoned baby.
At a town celebration, Buck falls for the daughter of an ambitious banker, but her motives in the relationship are questionable. Meanwhile, the Riders help a desperate woman whose husband was killed by the banker's henchmen, and they investigate accusations of illegal claim jumping.
When the Pony Express ownership wants to move the mail route north through Sioux burial lands, they send a college boy - Ambrose - to secure the arrangement. Ambrose has a serious case of hero worship for Hickok and, despite his naiveté, he refuses to be a pawn to anyone's manipulative plans.
Jimmy reunites with a friend and rival from his youth, Brad, both of whom trained under a Machiavellian mentor named Enright. When Enright's daughter goes missing, Jimmy helps Brad try to find her. But why did Clara really run away, and what does Enright have to do with corrupt land prospecting?
A corrupt businessman from Sam's violent past, Van Dorn, arrives in Sweetwater as the saloon's new owner. Van Dorn's henchmen are appointed as the town's new racketeering law enforcers, ousting Sam Cain as marshal. When Sam is accused of murder, Teaspoon, the Riders, a reluctant witness, and an alcoholic lawyer come to his aid.
When aging survivors of the Alamo are found murdered, one by one, Teaspoon and his old friend travel to Texas to get to the bottom of the killings. Jimmy and Buck follow in search of the truth and to lend a hand, and they learn that there is more to their mentor's past than they realized.
The Kid plays on his Virginia roots in order to infiltrate a gang of renegades led by an anti-government rebel named The Hawk. Meanwhile, an ambitious and head-strong Army captain begins to crack down on dissent in Sweetwater in his own bid to reveal and capture The Hawk and his men.
In part two, Jimmy joins The Kid as infiltrators into The Hawk's gang, and Ike befriends an abandoned mail-order bride named Annie. When Captain Lewis will not listen to the Riders with regard to The Hawk's plans, the citizens of Sweetwater must take up arms to defend their town against the renegade onslaught.