The show was developed after 20th Century Fox approached Hart Hanson in 2004 with an idea for a forensics show, and producer Barry Josephson had originally purchased rights to make a documentary about forensic anthropologist Kathy Reichs before it became a scripted series.

Although Hanson was initially reluctant to make a police procedural, he signed on and wrote the pilot, and the writers continued to involve Kathy Reichs in developing episode storylines throughout the show's run.

Kathy Reichs has stated she views the TV series as a kind of prequel to her novels, with the show's Temperance Brennan being a younger version of the character from her books.

David Boreanaz was the first actor cast, but he was initially unenthusiastic about joining after a difficult meeting with the producers; he only agreed after they contacted him again to convince him.

Hart Hanson said most actors who auditioned for Seeley Booth were 'pretty boy waifs,' and he immediately responded when studio head Dana Walden suggested Boreanaz for the role.

Emily Deschanel was recommended for the role of Brennan by producer Jerry Bruckheimer after she finished filming Glory Road; she impressed Hanson during her audition by holding her ground when Boreanaz stepped closer to her in a tense scene, something Hanson said 90% of actors would not do.

Angela Montenegro's father is played by ZZ Top guitarist Billy Gibbons as a fictionalized version of himself, though the character is never actually named on screen.

Although Bones is set in Washington, D.C., most filming took place in Los Angeles, using the Natural History Museum in Los Angeles and USC's Wallis Annenberg Building for exterior shots, while the Jeffersonian Institute interiors were built on a soundstage at the 20th Century Fox lot in Century City.

The two-part fourth season premiere was filmed on location in London and Oxford, England.

The second season episode 'Player Under Pressure' was pulled from its scheduled broadcast after the Virginia Tech massacre because its plot involved the murder of a college athlete; it did not air until over a year later, in the third season.

A spin-off called Bones: Skeleton Crew, consisting of 26 two-minute episodes not featuring the main cast, was produced in partnership with Sprint Nextel and MasterCard in 2006; long considered lost, three episodes were rediscovered on the Internet Archive in 2025.

Almost every episode title alliteratively describes how the victim's remains were discovered or the episode's main plot device, such as 'The Prisoner in the Pipe' or 'The Recluse in the Recliner'.

A 2016 New York Times study of the 50 TV shows with the most Facebook Likes found Bones was most popular in scattered areas of the West Coast and less popular in places with large nonwhite populations.

In December 2025, Disney announced that Bones was among the TV series to surpass one billion hours streamed on Disney+ during that year.