In the series premiere, Montana marshal Seth Bullock executes a last act of justice and 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 the hardware boys. At the Grand Central Hotel, Brom Garret rethinks his recent investment, while his wife Alma medicates her anxieties. 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 cowardly murderer. With Jane off on a bender, Trixie is enlisted by Swearengen to help Alma with the Metz child and to keep her pliable to his purposes; Doc Cochran fears Cramed's illness might threaten the camp; Tolliver sends Cramed to take the air in the woods, where he meets Jane. Feeling that justice hasn't been served, 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 for the 'Deadwood Pioneer.'