After escaping with the help of their friends, Brisco and Bowler are pursued by Colonel March and his gang of assassins. With March and General Quarry about to enact a traitorous plot, Brisco and Bowler race to stop them.
The army puts Brisco and Bowler on trial for high treason following the events of a special mission to Mexico to rescue a kidnapped newspaper tycoons' daughter. Even as Brisco pleads their side of the story, however, it is apparent that someone is determined to have them found guilty...
When Socrates vanishes during his birthday party, Brisco & co. follow his trail to Midnightville, a town in which Socrates used to work as a lawyer. Soon people of the town start being murdered, each of them connected to an old murder trial which Socrates was involved in, and Brisco races to piece together the mystery before Socrates is the next body found.
Pete Hutter returns once again, this time dropping a baby in Dixie Cousins' arms before being captured by ninja from the Black Lotus clan. While taking care of the baby and looking into the group, Brisco discovers a very personal connection to the Black Lotus, and will stop at nothing to find them.
When Brisco and Bowler witness what seems to be Dixie Cousins robbing a coach while en route to Reno, they track down Dixie to investigate. Upon doing so, they end up involved in a fight between Dixie and her sister, Dolly, and a local mob attempting to monopolize the local casinos.
Brisco is assigned to transport an English spy, Emma Steed, to Mexico as part of an exchange. Trouble arises when it turns out there is an assassin aboard the stagecoach, sent to make sure Steed doesn't get to her destination.
A father reads his son a bed-time story from a dime novel, of how Brisco County and his "loyal sidekick" Lord Bowler brought in the notorious Ned Zed.
Brisco and Bowler pursue the last member of John Bly's gang, but are interrupted when a strange visitor arrives to tell them of the Orb, and Bly's plans for it.
Brisco and Bowler run afoul of two orphans, who are being hunted by the New York City mob because of their inheritance. The bounty hunters agree to help get the orphans to San Francisco, while Socrates looks into their origins to give them legal help.
Brisco and Bowler arrive in Hard Rock, and foil local thug Gage and his gang from breaking up the restaurant run by Bowler's ex-girlfriend Lenore. It turns out he's working for Roy Hondo who is running a protection racket. Brisco, Bowler, and a young gunslinger named Whip work together to try and take Hondo down.
Brisco receives a telegram from Professor Coles, and arrives to find a trap set by Bly to force Coles to lead him to the Orb. With Coles' daughter, Lillian, seeking the orb for her own purposes as well, Brisco and Bowler must race to stop Bly and save the professor.
Brisco and Bowler are invited to a gathering of bounty hunters. However, the bounty hunters start getting murdered one by one, "Ten Little Indians" style. The pair must figure out who is responsible, and how to stop them.
Doc McCoy, a member of Bly's gang, plans to steal an experimental cannon and use it to steal an Orb. McCoy happens to be the ex-husband of Dixie Cousins, and with her help (and the guise of Kansas Wily Stafford) Brisco works his way into McCoy's circle to try and thwart his plot.
While back on the trail of the Swill brothers, Brisco and Bowler rescue three mail-order brides making their way to Denver who had their dowries stolen by the Swills. The Swills' newest plan is to steal a bull sent from Madrid, Spain to Madrid, CA as a token of peace and hold it for ransom. After escaping from the Swills' mother Lil (who holds them responsible for the death of her son Gil, in No Man's Land), they manage to thwart the Swills in Madrid.
Brisco is on the trail of a Bly gang member who uses prototype motorcycles to carry out robberies.
When investigating a crooked bank manager, Brisco witnesses his murder at the hands of Big Smith, a member of Bly's gang thought to be dead. Accussed of this murder and given a bounty, Brisco chases after Big Smith to clear his name, all the while being pursed by a relentless female bounty hunter named Crystal Hawks.
A ruthless assassin, Winston Smiles, is on the trail of Dixie Cousins because of vital evidence that she has against his employer. Brisco and Bowler come to her aid, and the trail leads to a nunnery where Dixie hid the evidence.
Brisco returns to his hometown to help an old friend of the family, the town sheriff, deal with a villainous cattle baron. He also renews a relationship with the sheriff's daughter and his previous girlfriend.
Brisco is called upon by an old friend, a doctor, to serve as defense lawyer when the guy is accused of murdering a prominent citizen. Despite the hostility of the townsfolk, the sheriff, and the judge,who is disdainful of Brisco's Harvard roots, having graduated from Yale himself.
On the trail of Bly once more, Brisco is confronted by the ghost of his father, who hints at his mysterious destiny with the Orb, hints that there are other Orbs, and helps him to track down Bly. Brisco Jr. must also deal with his obsession with Bly, and decide which is more important: bringing in the outlaw or endangering innocent lives.
Blackbeard LaCutte, a member of Bly's gang, fancies himself a pirate of the land, and intercepts stagecoaches and wagons and "boards" them. Brisco and Bowler team up again to track him down when LaCutte steals a town's supplies, including the medicine necessary to cure a dying boy.
Brisco heads to Louisiana to capture Brett Bones, a member of Bly's gang who runs a riverboat gambling ring. With Bones holding a letter of immunity from the governor, however, Brisco and his allies are forced to weave a complicated plot in order to trap him.
Brisco manages to capture Jack Randolph, one of Bly's gang. However, he claims to be a different Jack Randolph. Socrates' sister Iphigenia arrives to defend him, and it turns out she was also in a romantic correspondence with him. Randolph is the real Randolph, and uses Iphigenia to break out and try to recover stolen treasure in a submerged town.
When a shipment of guns are stolen, Brisco is sent to Mexico to track them down and make sure they don't become involved in a fight between an evil dictator and revolutionaries. When he finds himself sympathetic with the revolutionaries, however, Brisco is torn between doing his job and helping a noble cause.
Brisco is ordered to chase after the Swill brothers, a gang who stole an experimental tank from the Army. When he is injured in pursuit, Brisco is taken to a town populated by only women. When the Swill brothers show up shortly after him, it's up to Brisco and his new allies to stop them.
Brisco tracks Bly to a distant town where his childhood friend, Donovan, is the sheriff. But it's a trap set by Bly, and the second Orb is nearby as well.
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When marshal Brisco County Sr. is gunned down by John Bly and his gang of outlaws, his son, bounty hunter Brisco County Jr., comes back from the East to gain revenge on the killers.