Matlock was created by Dean Hargrove, who also created the 1980s Perry Mason television films, and the show's format—identifying perpetrators and confronting them in court—closely mirrors that of Perry Mason.

The series marked Andy Griffith's return to a television series for the first time since The New Andy Griffith Show ended in 1971.

Ben Matlock's daughter Charlene was played by Lori Lethin in the pilot movie, but Linda Purl took over the role once the series went to air.

Don Knotts, Andy Griffith's co-star from The Andy Griffith Show, joined the cast as Matlock's next-door neighbor Les 'Ace' Calhoun starting in season three.

Several actors played different one-off characters before becoming regular cast members, such as Nancy Stafford appearing as a high-class prostitute in season one's 'The Seduction' before joining as lawyer Michelle Thomas, and Daniel Roebuck appearing as three separate characters across earlier seasons before becoming series regular Cliff Lewis in season seven.

Kene Holliday, who played private investigator Tyler Hudson, was fired after the third season due to drug and alcohol abuse, though he returned for a couple of recurring appearances in season four.

Ben Matlock consistently drives an all-gray Ford Crown Victoria throughout the series, a nod to Andy Griffith's long-standing association with Ford vehicles dating back to The Andy Griffith Show.

The show filmed in California for its entire run on NBC, requiring Andy Griffith to commute from his home in North Carolina to the West Coast; after moving to ABC, production relocated to EUE/Screen Gems Studios in Wilmington, North Carolina, to ease his travel burden.

Jake and the Fatman, a spin-off starring William Conrad and Joe Penny, originated from the season one two-part Matlock episode 'The Don' about Mafia don Nicholas Baron.