The lead role of Jessica Fletcher was originally developed for actress Jean Stapleton, who showed initial interest but ultimately turned it down, nearly derailing the project.

Angela Lansbury was cast after the producers, worried she wouldn't be interested in television, sent her the script; she immediately felt connected to the role of Jessica Fletcher.

Before landing the role, Lansbury had played Salome Otterbourne in Death on the Nile (1978) and Miss Marple in The Mirror Crack'd (1980), an Agatha Christie adaptation whose poor box office performance caused a planned trilogy of Miss Marple films starring her to fall through.

The show's title is a nod to Murder, She Said, the title of a 1961 film adaptation of Agatha Christie's Miss Marple novel 4.50 from Paddington.

Jessica Fletcher's maiden name, MacGill, was actually Angela Lansbury's own mother's maiden name.

The series was mostly filmed on sound stages at Universal Studios in Universal City, California, with exterior shots of the fictional Cabot Cove filmed in Mendocino, Northern California, and dockside scenes shot at Noyo Harbor in Fort Bragg.

Angela Lansbury's brother, Bruce Lansbury, served as producer on 88 episodes of the show and also wrote 15 episodes.

In 1988, at age 63, Lansbury considered leaving the series due to the grueling schedule, which had increased from seven to eight days per episode; as a compromise, she reduced her screen time for two seasons while spin-off characters like Harry McGraw, Dennis Stanton, and Michael Hagarty carried their own storylines.

William Windom, who played recurring character Dr. Seth Hazlitt starting in 1985, had earlier appeared as a different character (lawyer Sam Breen) in the season 1 finale, and also appeared as a separate character in Magnum, P.I., set in the same universe.

The show crossed over with Magnum, P.I. across two episodes: the 1986 Magnum episode 'Novel Connection' was concluded four days later by the Murder, She Wrote episode 'Magnum on Ice.'

Angela Lansbury holds the record for the most Emmy nominations (12, one per season) for Outstanding Lead Actress in a Drama Series without ever winning, which is itself a record.

When CBS moved the show from its long-held Sunday slot to Thursday for season 12 to compete with NBC's 'Must See TV' lineup, ratings plummeted; two special Sunday airings in January and February 1996 drew nearly twenty million viewers each, prompting CBS to return the show to its original Sunday timeslot for its final episodes.

A planned 2013 NBC reboot starring Octavia Spencer as an amateur sleuth was scrapped in January 2014 after Lansbury objected to reusing the title and producers decided only she could ever play Jessica Fletcher.

A film adaptation of the series has been in development at Universal Pictures since 2023, with Jamie Lee Curtis cast as Jessica Fletcher and Jason Moore announced as director in January 2026.