The year is 1876 and the mining camp of Deadwood (in the Dakota Territory), grows in population from zero in March to over 10,000 in June. And with such a population explosion comes all kinds of prospectors, entrepreneurs and outlaws.

Ex-Montana lawman Seth Bullock (Timothy Olyphant) and his friend Sol Star (John Hawkes) arrive in the newly formed camp of Deadwood to start a hardware business. Also arriving in camp is ex-lawman and gunfighter Wild Bill Hickok (Keith Carradine), his friend Charlie Utter (Dayton Callie) and the colorful Calamity Jane (Robin Weigert). When news of a family being massacred on a road outside Deadwood reaches the group they set out to look for survivors.