Jess Harper rides into Laramie looking for a man but when he is met by a hail of bullets he heads for the country. There he runs into Slim Sherman and his young brother in a less than friendly manner but it leads to a new friendship.
When a man who saved Jess's life in the past arrives riding with a female preacher, Jess tries to avoid him but to no avail. Jess goes with them to Laramie where the man's lack of mental stability creates issues for everyone with him.
The stage arrives after a female passenger shoots a Pawnee who is the son of Chief Yellow Knife. The group is trapped at the relay station resulting in discord when they learn the woman is traveling with an ex-major accused of cowardice.
Jess's brother-in-law, an Army deserter, shows up looking for help to reach Canada via the Lola Pass. Slim is against Jess helping so he refuses to share his map of the trail. However, he relents under pressure against his better judgment.
A letter takes Jess to a town where he finds his friend has been killed but he develops a new friendship with the sheriff who ultimately hires Jess as a deputy. However, Jess is hurt when the sheriff strays due to a woman he desires.
Jess volunteers to go undercover for the sheriff and Army to pose as a guide for an outlaw hoping to locate the money from an earlier robbery. A He is one of five outlaws who each know only one leg of the route to the buried money.
Slim and Jess capture a ruthless outlaw and his partner but find themselves as his captives when the outlaw's gang break the outlaw loose during his trial. Slim is forced to retrieve the outlaw's girlfriend to save Jess - against her will.
When Ed Caulder appears, everyone is worried as he is a hired killer who receives his targets via General Delivery at the Post Office. At Laramie he asks for the Sherman ranch but an accident forces him to rely on his next target - Slim.
The beautiful Laurel DeWalt looking for a real man leaves her husband. She finds Jess who once had an affair with her. She wants him to take her to Mexico which he agrees to do. However, her husband sends three men after her.
Slim's civil war friend, Whit Malone, arrives on the stage. He offers Slim and Andy a chance to go fishing on his Montana ranch during their night of drinking. A sober Slim turns it down not realizing Whit's plan to kill General Sherman.
Jess's friend John MacLean is being chased by a posse for the murder of the sheriff and another man. They try to lynch him but Slim and Jess force a trial but the court is illegal. When John is lynched by them, Jess wants justice.
Father Elliott is on a mission to meet Sitting Bull at the same time the Sioux are on the warpath. After learning from a dying soldier the Sioux have modern firearms, he tells the Army. He then wants Jess to guide him to Sitting bull.
Anxious to help pay the bills at the financially-strapped station, Jonesy tries gold mining and piano playing during a gold strike. He then becomes the promoter for a traveling prizefighter whose bouts aren't always on the up-and-up.
Slim receives a letter for his dead father from a man threatening to kill him. Jonesy explains the man's son was killed fifteen years earlier in a stampede in which Slim was saved. Jonesy tries to smooth over things but it doesn't work.
At the same time Jess is bringing back the proceeds from a community wide cattle drive, Slim leases a rough section of the ranch to an ex-lawman who was a friend of his dad. Unknown to Slim, the lawman's hands are a rough bunch of outlaws.
When the Sioux and Cheyenne go on the warpath, they are forced to shutdown the relay station and leave. Jess is a scout for Custer while Slim is scout for a troop sent with supplies and dynamite to block a pass but their contact is dead.
A drought and the end of the stage line force Slim and Jess to join a cattle drive run by a stranger with their own herd in order for the ranch to survive. Jess is impressed with the hard nosed trail boss but they soon become suspicious.
Jess is a special deputy bringing Gabe Reynolds from Cheyenne to Laramie for murdering his wife. They are on the stage with four other passengers when the stage is overturned by a group of Mexicans wanting Gabe for the same murder.
Excitement comes to Laramie with the arrival of singer Lily Langford. Jonesy met her once while Jess and Slim tangle with Texan Shanghai Pierce who is after her husband Ben Carson who cheated him and others at cards and on paying bills.
A stage arrives with passengers that want to continue on at the same time a twister is supposed to hit the area. One of the passengers is hurt when Slim has to hit him when he pulls a gun. They are followed by a hit man who is after him.
At the same time the relay station horses are stolen, a new manager on the stage line, Jack Slade, arrives wanting Jess fired due to his background. Slade has a dark reputation for killing criminals with no compassion for anyone.
Mace Stringer stops a robbery but finds over $9,000 and the couple it belongs to shot. The robber escapes but Mace takes the mortally wounded husband to Laramie. Slim helps catch the killer but when the money disappears Mace point to Slim.
Jess responds to a letter for Slim from T.J. Patterson who needs help. After a reception of lead, Jess learns Patterson wanted Slim to recover stage line money stolen from him. He reluctantly agrees to help as Patterson helped Slim before.
Slim takes on the responsibility of the paroled Frank Buckley who was convicted of manslaughter for a rancher's war hero son's death. He is not wanted in the community which puts Slim and Jess in the middle of a war over him staying.
After a Laramie deputy is killed during a bank robbery, Slim continues the pursuit of the robber alone in the desert with limited water. He wounds the killer who then attaches himself to a stranded wagon with a desperate couple.
Billy Pardee is caught after a robbery and killing a deputy in Laramie. The posse decides his gang is returning to Laramie to break him out. When the Sheriff is wounded, he names Slim and Jess to take over the trial and hanging of Billy.
Slim and Jess are drawn into a fight brewing between the ranchers and nesters. The nesters have hired Gil Craig and his crew to protect them which is forcing the ranchers to act. Gil's designs on a lead rancher's wife results in murder.
During a time of low cattle prices, Slim and Jess leave to find a better price. Having no luck they find themselves in Agate, Nebraska broke. With their marshal killed, the town hires the pair to do the job for a month for good pay.
Jess's surprises everyone when he shoots a marshal in Laramie after knocking out Slim. On the lam he runs into a man who saw the shooting. Seeing an able but desperate Jess, the man offers him a job in a private army on the border.
Slim taking an injured Jonesy to town stops a fight between a man on a wagon train and the local blacksmith. In doing so the assistant wagon master loses face. In town the assistant sets up the man for a fight and Slim has to shoot him.
Jess is riding as deputy with a marshal chasing a gang to a private fort on the Santa Fe trail in the desert of New Mexico. The outlaw gang takes one of the men from the fort as hostage wanting the marshal and the wounded Jess in return.