The series is the second television adaptation of Ron Howard's 1989 film Parenthood, following an unsuccessful 1990-1991 NBC series that was cancelled after one season.

After creating Friday Night Lights, Jason Katims approached Ron Howard and Brian Grazer with the idea of making a modern, updated television adaptation of the 1989 film, and they eventually agreed despite initial reluctance.

Craig T. Nelson joined the cast as Zeek Braverman after turning down the role of Jay Pritchett in Modern Family.

Diane Farr was originally cast as Kristina Braverman but left due to scheduling conflicts with Californication and was replaced by Monica Potter.

Maura Tierney was originally cast in a lead role and had already filmed scenes, but she left the show in September 2009 due to conflicts with her breast cancer treatment schedule, and her footage was deleted; Helen Hunt was considered as a replacement but no financial deal could be reached with NBC, and Lauren Graham was ultimately cast instead.

The role of Hank Rizzoli was specifically written for Ray Romano after he told Jason Katims, whom he met on the set of Friday Night Lights, how much he loved the show.

The pilot episode was filmed in Northern California with local crews, while the rest of the series was shot in Los Angeles; the pilot had to be reshot in November 2009 following Tierney's departure.

As in Katims's other series Friday Night Lights, Parenthood was shot with three cameras placed on both sides of a scene, and episodes usually had no table reads before filming, unlike most television productions.

To ensure an accurate portrayal of Asperger's syndrome, actor Max Burkholder regularly met with a specializing doctor, along with the executive producer, director and writers, to discuss how his character Max would react in various situations.

Andrew McMahon of Jack's Mannequin wrote the song 'Casting Lines' after being contacted by the show's producers as a possible theme song, but the show ultimately chose Bob Dylan's 'Forever Young' instead; McMahon's song later appeared on his band's album People and Things.

The series premiere was dedicated to the memory of Nora O'Brien, an NBC vice president who died on the set of Parenthood on April 29, 2009, after collapsing from an aneurysm.

An Italian adaptation of the series titled Tutto può succedere (Anything Can Happen), following the Ferraro family in Rome, began airing on RaiUno in December 2015.