Acting for Two: Lansbury played both main character Jessica Fletcher and her cousin Emma McGill in the episodes "It Runs in the Family" and "Sing a Song of Murder". She also plays her Antebellum South era ancestor, Sarah McCollough, in "The Last Free Man" tv movie.
The very first episode starts with Jessica Fletcher watching the rehearsal of a murder mystery play and calmly pointing out who did it by the end of the first act. Angela Lansbury did much the same thing at the beginning of the 1980 film adaptation of The Mirror Crackd, in the role of Miss Marple.
"Sticks and Stones" features Parker Stevenson — aka Frank Hardy — as Michael Digby, a travel book writer/photographer. At one point Michael is trying to show his photos to a very disinterested Jessica (which is funny enough, as Parker is a professional photographer in real life), Jessica asks him if he would like to play detective for her...
Michael: Play a detective? Me??? YEAH!!!
"Trial by Error": There's something realironic about Brock Peters as a juror most steadfastly convinced that the man on trial is guilty.
"Birds of a Feather": Jeff Conaway as a man who used to be an aspiring actor who drove a taxi.
John Vernon ironically has a non-faculty role in "School for Scandal".
The exterior shots of Cabot Cove were filmed in the town of Mendocino (about halfway between San Francisco and the Oregon border).
"Witness for the Defense" is supposedly set in Quebec, but some interior scenes are shown to have green-lettered exit signs (the norm in California). Virtually all Canadian exit signs in that style are red.
Defictionalization: An official series of Murder, She Wrote novels claiming to be written by Jessica Fletcher "with Donald Bain" started in 1989 and continues to this day.
In "Murder at a Discount", George Segal's character is named Dave Navarro.
Screwed by the Network: Happened during the 12th and final season. The show had spent most of its run on Sunday nights and had gotten excellent ratings in the process. However, after Leslie Moonves became president of CBS Entertainment in 1995 before the 12th season began, he moved it to Thursday nights opposite Friends, a show that, ironically, he had previously helped to produce back when he was president of Warner Bros. Television. Many longtime fans of Murder, She Wrote angrily protested the scheduling change, and openly suspected Moonves of deliberately making the move in order to kill the show and, therefore, make room for new programs which he had greenlit.
Song Association: If you listen to the opening scene of "No Accounting for Murder", you'll hear an instrumental version of "New York, New York" playing.
Technology Marches On: During the run of the show, Jessica goes from typing manuscripts on a typewriter to using a computer, as reflected in updated opening credits. The final movie shows that Jessica has even begun using a laptop.
The pilot episode, "The Murder of Sherlock Holmes," becomes an Unintentional Period Piece thanks to this trope. When Jessica encounters the two young thugs in the alley, she threatens to call the police, but one of the thugs points out that it would be impossible for her to do so because she couldn't possibly have a phone in her purse.
What Could Have Been: Jean Stapleton, better known as Edith Bunker, was first offered the role of Jessica Fletcher. Stapleton passed - ironically, given that she's on record as being unhappy with her Typecasting as Edith, and this show likely would have rescued her from that fate. In any event, the producers then offered the role to their second choice, Angela Lansbury, who gratefully accepted.
This even happens with recurring guest stars. Ron Masak, before joining the cast as Sheriff Mort Metzger, appeared in two earlier episodes (the first playing a cop in New York!).
William Windom played one of the guilty party in "Funeral at Fifty-Mile" before appearing as Dr. Seth Hazlitt in the second season.
Madlyn Rhue, before playing Cabot Cove's librarian in later seasons, appeared earlier as a victim's widow in "Seal of the Confessional".
Another interesting example is "Murder on Madison Avenue": Firstly, after having played Jonathan Quayle Higgins in the aforementioned Crossover with Magnum, P.I., John Hillerman appears in this episode as a completely different character, to the likely confusion of longtime viewers. Secondly, Barbara Babcock's character (her fourth on MSW, fifth if you count The Law and Harry McGraw) is murdered by her assistant (played by Hallie Foote), but in an interesting possible Casting Gag, the next season episode "For Whom the Ball Tolls" sees Babcock and Foote together again (playing completely different characters, of course), working together on a historic preservation committee, as if nothing had ever happened.
Leslie Nielsen appears in the first season as the captain of a cruise ship when Jessica gets involved with a murder aboard the ship. He turns up again in season three as an old admirer of Jessica's who spots her on the street, plants a huge kiss on her lips, then shortly after gets accused of murder.
JaneLeeves shows up in season four episode "It Runs in the Family" as Gwen Petrie.