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.