The character of Special Agent G. Callen was originally created by Shane Brennan as a CIA operative for a separate series that was never produced; Brennan repurposed the concept when he took over showrunning duties on NCIS from Donald P. Bellisario.

Brennan envisioned the spin-off with a Miami Vice-esque vibe centered on co-leads Callen and Sam Hanna, but the backdoor pilot introduced the character of Lara Macy as a parallel to Gibbs, the lead of the original NCIS team.

Louise Lombard played Lara Macy in the two-part backdoor pilot, but she was not carried over to the actual series; her character was instead killed off in an NCIS episode as part of a vendetta against Gibbs.

During production, the series was internally known as NCIS: Legend (referencing the introductory NCIS episodes), and other considered titles included OSP: Office of Special Projects, NCIS: OSP, and NCIS: Undercover.

Filming began in February 2009, and the characters were first introduced in the two-part NCIS episode 'Legend,' whose first part aired on April 28, 2009, serving as a backdoor pilot similar to how NCIS itself was launched via a two-part JAG episode.

NCIS creator Donald Bellisario sued CBS in April 2011 over NCIS: Los Angeles, claiming his contract gave him 'first opportunity' to develop any spin-off or sequel; the lawsuit was dismissed in 2012, and the dispute was later settled out of court in January 2013 shortly before trial.

The Owen Granger storyline about the character developing cancer in season 8 coincided with actor Miguel Ferrer's real-life battle with cancer; following Ferrer's death, the character was written out and later confirmed to have died from his illness.

A potential second spin-off, NCIS: Red, was announced in November 2012 and introduced via a two-part NCIS: Los Angeles episode, but CBS officially passed on the project in May 2013; actor Scott Grimes still reprised his intended NCIS: Red role of Dave Flynn during the eighth season.

The series featured crossover appearances with Hawaii Five-0, as well as guest appearances from original NCIS cast members and characters from JAG, such as Harmon Rabb Jr. and Sarah MacKenzie, reprised by David James Elliott and Catherine Bell.