The series originated when Fred Silverman, CBS's programming chief who had cancelled The Beverly Hillbillies, asked producer Quinn Martin to create a detective show for Buddy Ebsen, recognizing the actor's appeal despite cancelling his previous sitcom.

Barnaby Jones's premise was originally conceived as a Cannon episode about a retired detective returning to work after his son's murder, intended as a spinoff launch, before Silverman reworked it into the first episode of a new series premiering as a midseason replacement in January 1973.

Before settling on its final title, the show went through several proposed names, including Parrish, Barnaby Cobb, and Barnaby Flint; Ebsen rejected Barnaby Cobb fearing critics would mock it by referencing Jed Clampett's corn cob pipe from The Beverly Hillbillies.

Ebsen had actually pitched producer Roger Gimbel his own idea for a seafaring private detective series in the style of Sam Spade, but Gimbel was busy with another project, which left an opening for Quinn Martin to offer Ebsen the Barnaby Jones role instead.

Composer Jerry Goldsmith wrote the show's musical theme only after music supervisor John Elizalde's first choice, composer and conductor André Previn, turned down the job.

To prepare for the role, Buddy Ebsen visited the Criminalistics Division of the Los Angeles County Sheriff's Department, where he learned to use a stereoscopic microscope and other forensic equipment to add authenticity to his performance.

After a few seasons, Ebsen asked CBS and producer Quinn Martin to reduce his workload so he could spend more time with his family at his wife's request; starting in season six, Ebsen led 12 episodes per season while Lee Meriwether and Mark Shera each led six.

Despite being scheduled against tough competition including the TV premiere of Lawrence of Arabia and NBC's Hec Ramsey, the debut episode of Barnaby Jones won its time slot and ranked 18th most popular show of the week, defying critics' predictions of early cancellation.

Although rumored for cancellation in multiple seasons, Barnaby Jones was not cancelled due to poor ratings but because CBS replaced it in 1980 with a new detective show starring Tom Selleck, Magnum, P.I., despite the show still performing well, particularly among older viewers.

Barnaby's advanced age (about 70 in-universe) was notable enough that the character was cited in a 1977 US House of Representatives hearing on age stereotyping on television, with a CBS executive praising Barnaby as a rare positive elderly character on prime-time TV.

A fan club called the Barnaby Jones Luncheon Club formed in New York in the early 1980s and grew to over 800 members by the late 1980s, meeting weekly for lunch; former President Richard Nixon, a friend of Ebsen's, was a member.

The show's exterior shots of Barnaby's detective agency actually depict the former Pacific Southwest Trust & Savings Bank building in Pasadena, not the agency's supposed downtown Los Angeles location.

Two episodes were designed as backdoor pilots for potential spinoff series—'A Ransom in Diamonds' and the series finale 'The Killin' Cousin'—but neither was developed into its own show.

Ebsen reprised the character of Barnaby Jones in the 1993 feature film The Beverly Hillbillies, which was his final theatrical film appearance; afterward, Lee Meriwether and Mark Shera expressed interest in a Barnaby Jones reunion TV movie, but could not convince Ebsen to join.