After executing a last act of justice as a Montana marshal, Seth Bullock relocates to a gold-mining camp known as Deadwood, where he and partner Sol Star look to start a hardware business. Bullock soon crosses paths with another new arrival - legendary gunfighter Wild Bill Hickok - and clashes with the formidable boss of the Gem Saloon, Al Swearengen. For his part, Swearengen must handle the deadly result of a run-in between one of his whores and a trick, while brokering the sale of a gold claim to wealthy New York socialite Brom Garret. When reports come of the massacre of a frontier family by Indians, a suspicious Bullock and Hickok ride out in search of survivors; for Swearengen, the results are bad for business.

As suspicions arise that "road agents" may have been the true perpetrators of the massacre, Swearengen takes a special interest in the health of its sole survivor, a young girl ministered to by the unlikely team of Doc Cochran and Calamity Jane. Meanwhile, Bullock and Star attempt to buy property from Swearengen, who suspects an alliance between Hickok and these hardware boys. At the Grand Central Hotel, Brom Garret rethinks his recent investment, while his wife Alma medicates her anxieties. And as a confrontation brews over the young survivor, Hickok asks Bullock to cover his back in a tension filled poker game.

Competition arrives for Swearengen in the form of the Bella Union, a new gambling outfit from Chicago operated by savvy Cy Tolliver, Madame Joanie Stubbs and gaming guru Eddie Sawyer. Hickok puts up precious collateral in a poker game with McCall; Bullock and Star strike a deal with Swearengen on a lot for their store and, with help from Hickok and Utter, set to building; Brom threatens Swearengen with The Pinkertons before he and Dan Dority are dispatched to reconnoiter his claim.

Swearengen directs Farnum to buy back the Garret claim; Alma prevails on Calamity Jane and Hickok for help; Hickok commissions Bullock in his stead; Charlie Utter leaves the camp; an ailing colleague, Andy Cramed, rejoins the Bella Union; and Hickok's run of luck at poker yields an unexpected return.

Swearengen transforms the Gem into a courtroom as Deadwood is forced to make its own laws to try a murderer; with Jane off on a bender, Swearengen employs Trixie to help Alma with the Metz Child; Doc Cochran fears Cramed's illness might threaten the camp; Tolliver sends Cramed to take air in the woods, where he meets Jane; and Bullock decides to take the law into his own hands.

Bullock encounters native resistance in his quest to bring a murderer to justice. Swearengen presses a resentful Farnum to keep tabs on Alma and Trixie; the camp fathers pool their resources to dispatch riders after precious vaccine and build a sick tent; Cochran enlists Jane as a nurse; and Swearengen collaborates on an article appearing in the Deadwood Pioneer.

After tracking down a murderer, Bullock returns to Deadwood a changed man--and a marked one--while Utter must pay final respects to a fallen friend. Dority and Stubbs both take special interest when teenagers Miles and Flora Anderson arrive in camp in search of their father, each finding work at a rival saloon; Calamity Jane earns her moniker in the Pest Tent; Swearengen sees through Trixie's latest subterfuge; and Alma remains cold on Farnum's inappropriately advanced bid on her claim.

Deadwood breathes easier when riders arrive with precious vaccine--and word of a possible treaty with the Sioux. Awaiting Trixie's return, a pragmatic Swearengen resists counsel from a bloody-minded Farnum; results of Bullock's assay of her gold claim moves Alma to reassess her plans and sets up a confrontation between Bullock and Swearengen; and Tolliver teaches Stubbs a deadly lesson at the expense of a couple of con artists.

With annexation looming, Swearengen calls a meeting to set up an informal government. Bullock and Alma compare notes on Ellsworth, and each other; Farnum gets a special-delivery letter from Hickok; Utter offers Jane a job; and Stubbs prepares to make a go on her own, with Tolliver's avowed blessings.

An opium theft leaves Swearengen trying to find common language with his supplier, as well as navigating tricky waters to deal with the mess. Meanwhile, Silas Adams, bagman for the magistrate from Yankton, arrives with bad news for Swearengen; Bullock regrets having raised his hand at the government meeting; Merrick proposes Deadwood's first "club"; and an unwelcome Rev. Smith gravitates to the Gem and its new piano.

Alma's father, Otis Russell, arrives from New York to "help" with her claim; Swearengen strikes a bargain with Adams to rid him of some legal baggage; Jewel journeys to Cochran's cabin for help with her leg; Utter hazards an opinion on the safety of Nuttal's saloon; Leon and Sawyer resume work at the Bella Union; Bullock is angered by the choice of a new sheriff; and Star winds up paying for a free service.

The U.S. Army--under General Crook a.k.a. "Custer's Avengers"--rolls into Deadwood, prompting a parade...and business solicitations from Farnum and Tolliver. Swearengen delivers a tortured soul from suffering; Bullock reacts decisively to Russell's intentions regarding Alma; Con Stapleton's new commission proves short-lived; Adams shows Clagett where his loyalties lie; and Bullock and Alma have a late-night meeting.