The series was first reported on in November 2019 and confirmed by Taika Waititi on Twitter shortly after, with Waititi co-writing alongside Native American filmmaker Sterlin Harjo, both sharing executive producer and directing duties.

Discussing their creative partnership, Waititi stressed that 'people need to tell their own stories and especially from whatever area they are from,' which led Harjo, who is from Oklahoma, to take the lead on the project while Waititi took a more supporting role.

Many of the storylines in the show are inspired by events from Sterlin Harjo's own childhood.

The series is the first American scripted show to feature an entirely Native writers' room, along with all Native American writers and directors and an almost entirely Indigenous North American cast and crew.

The four lead actors were cast from unknown Indigenous performers, including newcomer Lane Factor, and their casting was confirmed alongside the pilot's guest stars in December 2020 when FX ordered the series.

Leads Devery Jacobs and Paulina Alexis bonded during development over their mutual appreciation of the Indigenous sketch comedy group 1491s; four of the five members of the 1491s worked on season one, and with Ryan RedCorn joining the season two writers' room, all five members of the group ended up working on the show as writers, actors, directors, or producers.

The pilot was shot in Okmulgee, Oklahoma, and the entire first season was filmed in Oklahoma, marking a historic first for a scripted series to be filmed entirely in that state.

Principal photography for season one wrapped by July 2021 with filming locations across northeast Oklahoma including Okmulgee, Tulsa, Sand Springs, Beggs, Inola, and Terlton; season two was also filmed on location in Okmulgee.

Sterlin Harjo later created another FX series, The Lowdown, which he confirmed takes place in the same fictional universe as Reservation Dogs, with actors Ethan Hawke and Kaniehtiio Horn appearing in both shows as different characters.

The series premiered on FX on Hulu on August 9, 2021, deliberately chosen to coincide with the International Day of the World's Indigenous Peoples.